Ole Mathiesen

'Protective premedication': an option with gabapentin and related drugs? A review of gabapentin and pregabalin in the treatment of post-operative pain

Substantial progress has been made during the last decades in our understanding of acute pain mechanisms, and this knowledge has encouraged the search for novel treatments. Of particular interest has been the observation that tissue injury initiates a number of modulations of both the peripheral and the central pain pathways, which convert the system from a ‘physiological’ to a ‘pathological’ mode of processing afferent information. Gabapentin, which binds to the α2δ subunit of the voltage‐dependent calcium channel, is active in animal models of ‘pathological’ but not in models of ‘physiological’ pain. Consequently, attention has so far been focused on neuropathic pain as a target for the clinical use of gabapentin and analogues. Recently, several reports have indicated that gabapentin may have a place in the treatment of post‐operative pain. This article presents a brief summary of the potential mechanisms of post‐operative pain, and a systematic review of the available data of gabapentin and pregabalin for post‐operative analgesia. It is concluded that the results with gabapentin and pregabalin in post‐operative pain treatment published so far are promising. It is suggested that future studies should explore the effects of ‘protective premedication’ with combinations of various antihyperalgesic and analgesic drugs for post‐operative analgesia.

The transversus abdominis plane block: a valuable option for postoperative analgesia? A topical review

The transversus abdominis plane (TAP) block is a newly described peripheral block involving the nerves of the anterior abdominal wall. The block has been developed for post‐operative pain control after gynaecologic and abdominal surgery. The initial technique described the lumbar triangle of Petit as the landmark used to access the TAP in order to facilitate the deposition of local anaesthetic solution in the neurovascular plane. Other techniques include ultrasound‐guided access to the neurovascular plane via the mid‐axillary line between the iliac crest and the costal margin, and a subcostal access termed the ‘oblique subcostal’ access. A systematic search of the literature identified a total of seven randomized clinical trials investigating the effect of TAP block on post‐operative pain, including a total of 364 patients, of whom 180 received TAP blockade. The surgical procedures included large bowel resection with a midline abdominal incision, caesarean delivery via the Pfannenstiel incision, abdominal hysterectomy via a transverse lower abdominal wall incision, open appendectomy and laparoscopic cholecystectomy. Overall, the results are encouraging and most studies have demonstrated clinically significant reductions of post‐operative opioid requirements and pain, as well as some effects on opioid‐related side effects (sedation and post‐operative nausea and vomiting). Further studies are warranted to support the findings of the primary published trials and to establish general recommendations for the use of a TAP block.

Adductor canal block versus femoral nerve block for analgesia after total knee arthroplasty: a randomized, double-blind study.

Background and Objectives Femoral nerve block (FNB), a commonly used postoperative pain treatment after total knee arthroplasty (TKA), reduces quadriceps muscle strength essential for mobilization. In contrast, adductor canal block (ACB) is predominately a sensory nerve block. We hypothesized that ACB preserves quadriceps muscle strength as compared with FNB (primary end point) in patients after TKA. Secondary end points were effects on morphine consumption, pain, adductor muscle strength, morphine-related complications, and mobilization ability. Methods We performed a double-blind, randomized, controlled study of patients scheduled for TKA with spinal anesthesia. The patients were randomized to receive either a continuous ACB or an FNB via a catheter (30-mL 0.5% ropivacaine given initially, followed by a continuous infusion of 0.2% ropivacaine, 8 mL/h for 24 hours). Muscle strength was assessed with a handheld dynamometer, and we used the percentile change from baseline for comparisons. The trial was registered at clinicaltrials.gov (Identifier: NCT01470391). Results We enrolled 54 patients, of which 48 were analyzed. Quadriceps strength as a percentage of baseline was significantly higher in the ACB group compared with the FNB group: (median [range]) 52% [31–71] versus 18% [4–48], (95% confidence interval, 8–41; P = 0.004). There was no difference between the groups regarding morphine consumption (P = 0.94), pain at rest (P = 0.21), pain during flexion of the knee (P = 0.16), or adductor muscle strength (P = 0.39); neither was there a difference in morphine-related adverse effects or mobilization ability (P > 0.05). Conclusions Adductor canal block preserved quadriceps muscle strength better than FNB, without a significant difference in postoperative pain.

Effects of Adductor-Canal-Blockade on pain and ambulation after total knee arthroplasty: a randomized study

Total knee arthroplasty (TKA) is associated with intense post‐operative pain. Besides providing optimal analgesia, reduction in side effects and enhanced mobilization are important in this elderly population. The adductor‐canal‐blockade is theoretically an almost pure sensory blockade. We hypothesized that the adductor‐canal‐blockade may reduce morphine consumption (primary endpoint), improve pain relief, enhance early ambulation ability, and reduce side effects (secondary endpoints) after TKA compared with placebo.

Adductor canal block versus femoral nerve block and quadriceps strength: a randomized, double-blind, placebo-controlled, crossover study in healthy volunteers.

Background:The authors hypothesized that the adductor canal block (ACB), a predominant sensory blockade, reduces quadriceps strength compared with placebo (primary endpoint, area under the curve, 0.5–6 h), but less than the femoral nerve block (FNB; secondary endpoint). Other secondary endpoints were adductor strength and ability to ambulate. Methods:The authors enrolled healthy young men into this double blind, placebo-controlled, randomized, crossover study. On two separate study days, subjects received either ACB or FNB with ropivacaine, and placebo in the opposite limb. Strength was assessed as maximum voluntary isometric contraction for quadriceps and adductor muscles. In addition, subjects performed three standardized ambulation tests. Clinicaltrials.gov Identifier: NCT01449097. Results:Twelve subjects were randomized, 11 analyzed. Quadriceps strength (area under the curve, 0.5–6 h) was significantly reduced when comparing ACB with placebo (5.0 ± 1.0 vs. 5.9 ± 0.6, P = 0.02, CI: −1.5 to −0.2), FNB with placebo (P = 0.0004), and when comparing FNB with ACB (P = 0.002). The mean reduction from baseline was 8% with ACB and 49% with FNB. The only statistically significant difference in adductor strength was between placebo and FNB (P = 0.007). Performance in all mobilization tests was reduced after an FNB compared with an ACB (P < 0.05). Conclusions:As compared with placebo ACB statistically significantly reduced quadriceps strength, but the reduction was only 8% from baseline. ACB preserved quadriceps strength and ability to ambulate better than FNB did. Future studies are needed to compare the analgesic effect of the ACB with the FNB in a clinical setting.

Gabapentin and postoperative pain: a qualitative and quantitative systematic review, with focus on procedure

BackgroundGabapentin is an antiepileptic drug used in a variety of chronic pain conditions. Increasing numbers of randomized trials indicate that gabapentin is effective as a postoperative analgesic. This procedure-specific systematic review aims to analyse the 24-hour postoperative effect of gabapentin on acute pain in adults.MethodsMedline, The Cochrane Library and Google Scholar were searched for double-blind randomized placebo controlled trials of gabapentin for postoperative pain relief compared with placebo, in adults undergoing a surgical procedure.Qualitative analysis of postoperative effectiveness was evaluated by assessment of significant difference (P < 0.05) in pain relief using consumption of supplemental analgesic and pain scores between study groups.Quantitative analyses of combined data from similar procedures, were performed by calculating the weighted mean difference (WMD) of 24-hour cumulated opioid requirements, and the WMD for visual analogue scale (VAS) pain, (early (6 h) and late (24 h) postoperatively), between study groups. Side-effects (nausea, vomiting, dizziness and sedation) were extracted for calculation of their relative risk (RR).ResultsTwenty-three trials with 1529 patients were included. In 12 of 16 studies with data on postoperative opioid requirement, the reported 24-hour opioid consumption was significantly reduced with gabapentin. Quantitative analysis of five trials in abdominal hysterectomy showed a significant reduction in morphine consumption (WMD – 13 mg, 95% confidence interval (CI) -19 to -8 mg), and in early pain scores at rest (WMD – 11 mm on the VAS, 95% CI -12 to -2 mm) and during activity (WMD -8 mm on the VAS; 95% CI -13 to -3 mm), favouring gabapentin. In spinal surgery, (4 trials), analyses demonstrated a significant reduction in morphine consumption (WMD of – 31 mg (95%CI – 53 to -10 mg) and pain scores, early (WMD – 17 mm on the VAS; 95 % CI -31 to -3 mm) and late (WMD -12 mm on the VAS; 95% CI -23 to -1 mm) also favouring gabapentin treatment. Nausea was improved with gabapentin in abdominal hysterectomy (RR 0.7; 95 % CI 0.5 to 0.9). Other side-effects were unaffected.ConclusionPerioperative use of gabapentin has a significant 24-hour opioid sparing effect and improves pain score for both abdominal hysterectomy and spinal surgery. Nausea may be reduced in abdominal hysterectomy.

Pregabalin and dexamethasone in combination with paracetamol for postoperative pain control after abdominal hysterectomy. A randomized clinical trial.

Background: Multimodal analgesia may be important for optimal postoperative pain treatment and facilitation of early mobilization and recovery. We investigated the analgesic effect of pregabalin and dexamethasone in combination with paracetamol after abdominal hysterectomy.

The Beneficial Effect of Transversus Abdominis Plane Block After Laparoscopic Cholecystectomy in Day-Case Surgery: A Randomized Clinical Trial

BACKGROUND: Laparoscopic cholecystectomy is associated with postoperative pain of moderate intensity in the early postoperative period. Recent randomized trials have demonstrated the efficacy of transversus abdominis plane (TAP) block in providing postoperative analgesia after abdominal surgery. We hypothesized that a TAP block may reduce pain while coughing and at rest for the first 24 postoperative hours, opioid consumption, and opioid side effects in patients undergoing laparoscopic cholecystectomy in day-case surgery. METHODS: In this randomized, double-blind study, 80 patients undergoing laparoscopic cholecystectomy in our day-case surgery unit were allocated to receive either bilateral ultrasound-guided posterior TAP blocks (20 mL 0.5% ropivacaine) or placebo blocks. Postoperative pain treatment consisted of oral acetaminophen 1000 mg × 4, oral ibuprofen 400 mg × 3, IV morphine (0–2 hours postoperatively), and oral ketobemidone (2–24 hours postoperatively). The primary outcome was postoperative pain scores while coughing calculated as area under the curve for the first 24 postoperative hours (AUC/24 h). Secondary outcomes were pain scores at rest (AUC/24 h), opioid consumption, and side effects. Patients were assessed 0, 2, 4, 6, 8, and 24 hours postoperatively. Group-wise comparisons of visual analog scale (VAS) pain (AUC/24 h) were performed with the 2-sample t test. Morphine and ketobemidone consumption were compared with the Mann-Whitney test for unpaired data. Categorical data were analyzed using the &khgr;2 test. RESULTS: The primary outcome variable, VAS pain scores while coughing (AUC/24 h), was significantly reduced in the TAP versus the placebo group (P = 0.04); group TAP: 26 mm (SD 13) (weighted average level) versus group placebo: 34 (18) (95% confidence interval): 0.5–15 mm). VAS pain scores at rest (AUC/24 h) showed no significant difference between groups. Median morphine consumption (0–2 hours postoperatively) was 7.5 mg (interquartile range: 5–10 mg) in the placebo group compared with 5 mg (interquartile range: 0–5 mg) in the TAP group (P < 0.001). The odds ratio of a random patient in group TAP having less morphine consumption than a random patient in group placebo was P (group TAP < group placebo) = 0.26 (confidence interval: 0.15, 0.37) where 0.5 represents no difference between groups. There were no between-group differences in total ketobemidone consumption, levels of nausea and sedation, number of patients vomiting, or consumption of ondansetron. CONCLUSIONS: TAP block after laparoscopic cholecystectomy may have some beneficial effect in reducing pain while coughing and on opioid requirements, but this effect is probably rather small.

Effect of adductor-canal-blockade on established, severe post-operative pain after total knee arthroplasty: a randomised study.

In this proof‐of‐concept study, we investigated the effect of the predominantly sensory adductor‐canal‐blockade on established pain in the early post‐operative period after total knee arthroplasty (TKA). We hypothesised that the adductor‐canal‐blockade would reduce pain during flexion of the knee (primary end point) and at rest, as well as reducing morphine consumption and morphine‐related side effects (secondary outcomes) compared with placebo.

Effect of adductor canal block versus femoral nerve block on quadriceps strength, mobilization, and pain after total knee arthroplasty: a randomized, blinded study.

Background and Objectives Total knee arthroplasty (TKA) is often associated with severe pain. Different regional anesthetic techniques exist, all with varying degrees of motor blockade. We hypothesized that pain relief provided by the adductor canal block (ACB) could increase functional muscle strength. Methods We included 50 TKA patients with severe movement-related pain; defined as having visual analog scale pain score of greater than 60 mm during active flexion of the knee. The ACB group received an ACB with ropivacaine 0.2% 30 mL and a femoral nerve block (FNB) with 30 mL saline. The FNB group received an ACB with 30 mL saline and an FNB with ropivacaine 0.2% 30 mL. We compared the effect of the ACB versus FNB on maximum voluntary isometric contraction of the quadriceps muscle relative to a postoperative baseline value. Secondary end points were differences between groups in ability to ambulate and changes in pain scores (Clinicaltrials.gov identifier NCT01922596). Results After block, the quadriceps maximum voluntary isometric contraction increased to 193% (95% confidence interval [CI], 143–288) of the baseline value in the ACB group and decreased to 16% (95% CI, 3–33) in the FNB group with an estimated difference of 178% (95% CI, 136–226), P < 0.0001. Pain scores were similar between groups. Before block, 2 of 25 patients in each group were unable to perform the Timed-Up-and-Go test; after block, this number increased to 7 of 25 in the FNB group and decreased to 0 of 25 in the ACB group. Conclusion Adductor canal block provides a clinically relevant and statistically significant increase in quadriceps muscle strength for patients in severe pain after TKA.