Gabapentin For Postoperative Pain Research Articles

Gabapentin for Postoperative Pain

Scores of studies have been performed to examine whether short-course gabapentin and pregabalin mitigate pain after various surgical procedures;

Preemptive versus postincision gabapentin for postoperative pain: systematic review and meta-analysis

Preemptive versus postincision gabapentin for postoperative pain: systematic review and meta-analysis

Effect of gabapentin in postoperative pain, nausea, and vomiting in patients undergoing laparoscopic cholecystectomy

Background: Postoperative pain, nausea, and vomiting are frequent and unpleasant adverse events associated with surgery. The reported incidence of postoperative nausea and vomiting after laparoscopic cholecystectomy (LC) is quite high. Recently, studies have been undertaken to determine the role of gabapentin for the prevention of postoperative pain, nausea, and vomiting. Objective: To evaluate the effects of oral gabapentin on early postoperative pain, nausea, and vomiting in patients undergoing LC. Materials and Methods: A total of 40 patients scheduled to undergo LC were enrolled for this double-blind placebo-controlled study. Patients were divided into two groups of 20 patients each. Group A received two doses of 600 mg (300 mg ± 2 tablets) gabapentin: first dose 2 h before surgery and second dose 6 h after surgery. Group B received matching placebo (tablets) of same size and shape as gabapentin tablets. All patients were observed for postoperative pain, nausea, and vomiting on first and second postoperative days. In addition, pulse rate and systolic and diastolic blood pressures were analyzed pre- and postoperatively. Injections ondansetron and diclofenac were used as the antiemetic and analgesic medications, respectively, on as-and-when required basis. Results: Intergroup comparison with respect to pulse rate and systolic and diastolic blood pressures between the two groups was insignificant (p > 0.05). On the first and second postoperative days of LC, average numbers of analgesics used in gabapentin group were 1.2 ± 0.13 and 0.65 ± 0.15 and in placebo group were 2.6 ± 0.10 and 2.2 ± 0.16, respectively. Intergroup comparison was highly significant (p < 0.001). The average number of antiemetics received on first and second postoperative days in gabapentin group was 0.35 ± 0.1 and 0.05 ± 0.04 and in placebo group were 1.31 ± 0.16 and 0.60 ± 0.15, respectively. Intergroup comparison was highly significant (p < 0.001). Pain score in gabapentin group on first and second postoperative days was 2.6 ± 0.17 and 2.2 ± 0.15 and in placebo group 3.80 ± 0.81 and 3.2 ± 0.17, respectively. Intergroup comparison was highly significant (p < 0.001). Conclusion: Administration of gabapentin 2 h before and 6 h after the surgery significantly decreased the incidence of postoperative pain, nausea, and vomiting.

The Importance of Perioperative Administration of an Anti-Hyperalgesic Drug in Burn Wounds

Dear Editor, We read with interest the article by Rimaz and coworkers about the beneficial effect of preoperative oral administration of a high single dose (1200 mg) of gabapentin on postoperative pain scores and morphine consumption in patients undergoing surgical debridement of burn wounds (1). The effect of preoperative administration of oral gabapentin in order to reduce postoperative pain scores and opioid consumption was analyzed in several studies. A systematic review of randomized controlled trials published by Ho and coworkers has shown that, in different types of surgery, the preoperative administration of a single dose of 1200 mg oral gabapentin produced a significant reduction in pain intensity at rest compared with placebo in the early and late postoperative period at 6 and 24 h after administration, respectively. In addition, some similar studies showed a significant reduction in opioid consumption and a delayed request for analgesia (2). As regard to the adverse effects, the administration of 1200 mg of oral gabapentin did not show significant differences with respect to placebo in a large part of published studies. Indeed, as highlighted by Turan and coworkers, the treatment group showed fewer episodes of vomiting and urinary retention, probably due to lower consumption of opioids in the postoperative period (3). However, administration of a single dose of 1200 mg of oral gabapentin in the preoperative period showed no serious adverse effects in the treated patients. The analysis of available data has revealed a number of limitations, in particular due to the different type of surgery. An interesting systematic review published by Mathiesen et al. focused on the use of gabapentin in the preoperative period in relation to the surgical procedures. Reported data showed that preoperative gabapentin administration in different dosages appears to be particularly effective in reducing postoperative opioid consumption particularly after abdominal hysterectomy and spinal surgery, while the use in other sort of surgeries revealed no significant results. In addition, a reduction in pain scores was demonstrated mostly in early postoperative period, probably due to higher gabapentin plasmatic level in the early postoperative phase (4). At a single preoperative oral dose of 1200 mg, gabapentin showed conflicting results in relation to different types of surgeries, with promising evidences only in abdominal hysterectomy, spinal surgery, radical mastectomy, thyroid and ear-nose throat surgery. However, these results should be confirmed by further investigations using the same methodology, in particular with respect to the type of anesthesia and rescue analgesia in the postoperative period. Currently, there are no other publications on the use of preoperative gabapentin in postoperative pain in burned patients. In this regard, we agree with the authors that the burn wounds, in relation to the particular type of damage, may benefit from perioperative administration of an anti-hyperalgesic drug. In fact, some nerve endings of skin nociceptors after burns are still intact or only partially injured and continue to generate pain impulses leading to primary hyperalgesia (5). However, further studies are needed to confirm these results, especially focused on the dose-response relationship of preoperative gabapentin, looking for the lowest effective dose.

Control of Pain After Surgical Debridement of Burn Wounds

Dear Editor, We read with interest your article on the use of gabapentin pain control after burn debridement (1). Gabapentin has a well-established role in the management of neuropathic pain, and has been investigated in the past decade regarding its ability to potentiate the effect of morphine on postoperative pain, or decrease the amount of pain experienced by patients after surgery. This study represents one of the only randomized, placebo-controlled, double-blind studies to look at gabapentin in burn patients. The authors found that 1200mg of gabapentin 2 hours prior to operative debridement of burn wounds led to a significant decrease in pain in the immediate 24-hour postoperative period, as measured by the visual analog score and by patient-requested morphine consumption. While the results are important and consistent with the growing body of literature, there remain methodological questions that are not addressed (2-4). First, while the authors state that total burn surface area in all patients were comparable (average of 13% ± 25 in the placebo group versus 19% ± 29 in the gabapentin group), there are several additional characteristics that can significantly affect pain, both pre-and post-operatively. Burn severity, type of burn (flame, chemical) and location on the body are not addressed here. In addition, the extent of debridement must also be considered, with regard to both surface area and depth. Conditions such as infection or other complicating medical conditions are also not mentioned in the article, which can be common in burn patients, and which can significantly affect patient outcome. Secondly, neuropathic pain induced by burns can lead to chronic and debilitating pain; this should be evaluated, depending on the feasibility of follow-up. The authors state that “Fassoulaki et al. (5) were unable to demonstrate a decrease in analgesic consumption and VAS scores at rest or after movement during the first 24h after the operation” due to “differences in the types of surgeries performed.” In fact, however, Fassoulaki et al. (5) were able to find that gabapentin reduced requirement for analgesics and led to decreased pain with movement within the first week post-operatively; the caveat was that this difference did not persist long-term (at 10 days or 3 months). Because chronic pain control can be such an important aspect of clinical outcomes in burn patients, this is critical to consider when thinking about impact on changes in management. In summary, this study provides important support for the use of gabapentin in postoperative pain, and represents one of the only studies to address its use in burn patients. However, several questions regarding the clinical condition of patients (burn severity, type of burn, location of burn, extent of debridement, and presence of infection) must be considered; long-term sequelae with regard to chronic pain must also be addressed. All of these variables must be taken into account before the true impact of gabapentin in these patients can be determined.

Gabapentin for Postoperative Pain After Photorefractive Keratectomy: A Prospective, Randomized, Double-blind, Placebo-controlled Trial

To determine whether treatment with oral gabapentin reduces postoperative pain after photorefractive keratectomy (PRK). This prospective, randomized, double-blind, placebo-controlled study comprised 40 patients scheduled for bilateral PRK. Exclusion criteria were previous refractive surgery; diseases that could affect epithelial healing; use of antihistamines, nonsteroidal anti-inflammatory drugs, or steroids; and use of mitomycin C during PRK. Patients were divided into two groups: 20 patients received gabapentin capsules (300 mg) and 20 patients received identical placebo capsules. Visual acuity, slit-lamp examination, and a 12-question, 10-point visual numerical scale questionnaire were evaluated at each postoperative follow-up. Main outcome measures were the severity of pain at each follow-up and during the previous 24 hours. Secondary outcome measures were maximum and minimum severity of pain, healing time, uncorrected distance visual acuity, and the rating of other symptoms and potential side effects. The gabapentin group had less pain during the first 72 hours (P=.024 to .001). A significant difference in favor of gabapentin was found for the first 48 hours regarding minimum pain severity (P=.005 and .01 for 24 and 48 hours, respectively) and for the first 72 hours for maximum pain severity (P=.014, .007, and .001 for 24, 48, and 72 hours, respectively). No significant differences were observed for side effects, symptoms, or healing time except discomfort in favor of gabapentin during the first 24 hours (P=.043). Gabapentin significantly reduced postoperative pain after PRK compared to placebo, with no increase in reported side effects.

A randomized controlled trial to compare pregabalin with gabapentin for postoperative pain in abdominal hysterectomy

Background:Pregabalin is a potent ligand for alpha-2-delta subunit of voltage-gated calcium channels in the central nervous system, which exhibits potent anticonvulsant, analgesic and anxiolytic activity. The pharmacological activity of pregabalin is similar to that of gabapentin and shows possible advantages. Although it shows analgesic efficacy against neuropathic pain, very limited evidence supports its postoperative analgesic efficacy. We investigated its analgesic efficacy in patients experiencing acute pain after abdominal hysterectomy and compared it with gabapentin and placebo.Methods:A randomized, double-blind, placebo-controlled study was conducted in 90 women undergoing abdominal hysterectomy who were anaesthetized in a standardized fashion. Patients received 300 mg pregabalin, 900 mg gabapentin or placebo, 1–2 hours prior to surgery. Postoperative analgesia was administered at visual analogue scale (VAS) ≥3. The primary outcome was analgesic consumption over 24 hours and patients were followed for pain scores, time to rescue analgesia and side effects as secondary outcomes.Results:The diclofenac consumption was statistically significant between pregabalin and control groups, and gabapentin and control groups; however, pregabalin and gabapentin groups were comparable. Moreover, the consumption of tramadol was statistically significant among all the groups. Patients in pregabalin and gabapentin groups had lower pain scores in the initial hour of recovery. However, pain scores were subsequently similar in all the groups. Time to first request for analgesia was longer in pregabalin group followed by gabapentin and control groups.Conclusion:A single dose of 300 mg pregabalin given 1–2 hours prior to surgery is superior to 900 mg gabapentin and placebo after abdominal hysterectomy. Both the drugs are better than placebo.

Role of gabapentin in postoperative pain

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Antihyperalgesic Effects of Intrathecal Gabapentin and CNQX, Non-NMDA Receptor Antagonist, in a Rat Model for Postoperative Pain

Background: Although the descriptions of the pharmacological action mechanisms of gabapentin remain incomplete, gabapentin has been proven to provide analgesic effects in inflammatory, bum injury and neuropathic pain models. However, the analgesic effect of gabapentin in postoperative pain has not been demonstrated. Of the antagonists of the excitatory neurotransmitter receptor in the spinal dorsal horn, only the antagonists of the non-NMDA receptor have proven effective in a postoperative acute pain model. In the current study, the antihyperalgesic effects of intrathecal gabapentin and CNQX (6-cyano-7-nitroquinoxaline-2, 3-dione) were determined in a rat model of postoperative pain. Furthermore, the drug interaction when both drugs were co-administrated was also tested. Methods: A lumbar intrathecal catheter was implanted into Sprague-Dawley rats (weight 300-350 g) and the rats then assigned to receive one of several doses of gabapentin (10, 30, 100, 300 ), CNQX (1, 5, 10, 25 ) and gabapentin + CNQX (1/2 for each drug, 1/4 , 1/8 ), and the level of withdrawal threshold to the von Frey Filament near the incision site determined. The dose response curves were obtained, and the ED50 of each drug calculated. Isobolographic and fractional analyses were performed to study the drug interaction. Results: Both gabapentin and CNQX displayed dose dependent antihyperalgesic effects. The for gabapentin and CNQX were 56.2 (95% confidence interval [CI], 45.3 -69.7 ) and 4.6 (CI, 3.2 -6.5 ), respectively. When both drugs were co-administrated, the for gabapentin and CNQX were 23.4 (CI, 20.2 - 27.1 ) and 1.6 (CI, 1.3 -1.8 ), respectively. In the fractional analysis, the fraction obtained using this numeric value was 0.77. In the isobologram analysis, the obtained value of the gabapentin-CNQX mixture was below the theoretical additive value on the diagonal line, but this was not statistically significant. Conclusions: The intrathecal co-administration of gabapentin and CNQX showed an additive antihyperalgesic effect in our rat model of postoperative pain.

Gabapentin: The First Preemptive Anti-Hyperalgesic for Opioid Withdrawal Hyperalgesia?

Departments of Anesthesiology and Pharmacology &amp; Toxicology, Queen's University, Kingston, Ontario, Canada. gilroni@post.queensu.caIn Reply:—The above letter responds to the provocative question of whether gabapentin is a “broad spectrum” analgesic 1and appropriately points out that things are not quite so simple.Gustorff et al. postulate that the effects of gabapentin reported by Dirks et al. 2are not due to antinociception but, rather, to the suppression of hyperalgesia caused by withdrawal from intraoperative opioids. This is a reasonable hypothesis; however, it should be noted that Fassoulaki et al. recently observed similar reductions in pain and opioid consumption with gabapentin in patients who received no intraoperative opioids. 3Therefore, gabapentin's effects cannot be solely due to suppression of opioid withdrawal hyperalgesia.Nevertheless, this raises questions central to understanding the modulation of pain by gabapentin. While Gustorff et al. correctly indicate that postoperative pain is predominantly nociceptive, they fail to emphasize the importance of spinal sensitization, 4which contributes to hyperalgesia and allodynia and which may be suppressed by gabapentin. Indeed, although gabapentin has little antinociceptive effect in the uninjured organism, it has been shown, in the absence of opioids, to reduce pain responses after surgical tissue injury. 5The latter comments by Gustorrf et al. illustrate the complexities of interpreting gabapentin's effect when administered with opioids. Ethical conduct of most postoperative trials requires the provision of rescue analgesia, often in the form of patient-controlled analgesia with morphine, which necessitates the integration of pain measures with morphine consumption as co-relevant outcome measures. 6Although trials have been equivocal thus far, 7,8the possibility that mechanisms of opioid tolerance 9contribute to postoperative hyperalgesia and increased opioid requirements may confound results of analgesic trials. Therefore, gabapentin trials involving concomitant morphine administration must be interpreted in light of a possible interaction between these drugs. In this regard, we have observed in the rat that gabapentin prevents the development of morphine tolerance and partially reverses established tolerance indicating that such an interaction indeed exists. 10Thus, although follow-up studies will further characterize the role of gabapentin in postoperative pain, even more sophisticated strategies are needed to distinguish between its specific pharmacological effects (e.g. , analgesia, antihyperalgesia, antiallodynia and reversal of opioid tolerance).