Sensory distribution of the lateral femoral cutaneous nerve block - a randomised, blinded trial.

BACKGROUND: The lateral femoral cutaneous nerve (LFCN) block may be used for post-operative pain management in patients undergoing total hip arthroplasty. The aim of this trial was to investigate the sensory coverage of the posterior and the lateral incision lines and the involvement of the femoral nerve after an LFCN block. METHODS: The study was a randomised, blinded trial in 20 healthy volunteers. All subjects received a bilateral LFCN block randomised to 8 ml ropivacaine on the right side and 8 ml isotonic saline on the left side, or vice versa. An orthopaedic surgeon depicted the incision lines (invisible to the investigators) prior to block performance. The distribution of the blocked area and the coverage of the incision lines were assessed with temperature discrimination and pinprick test before unblinding the incision lines. Pain during tonic heat stimulation and involvement of the femoral nerve by measuring quadriceps strength were assessed. RESULTS: The mean difference in block coverage of the posterior (primary outcome) and the lateral incision lines tested with temperature discrimination were 5.8% (95% CI: -2.2 to 14.0%, P = 0.146) and 18.9% (95% CI: 6.5-31.4%, P = 0.005), respectively, comparing the active with the placebo side. A varying anatomic distribution area was observed. No clinically significant differences for experimental pain and quadriceps muscle strength were found. The block failure rate was 15%. CONCLUSION: An LFCN block consisting of 8 ml 0.75% ropivacaine had limited coverage of the posterior and lateral incision lines.

Evolution of bias and sample size in postoperative pain management trials after hip and knee arthroplasty.

BACKGROUND: Bias (systematic error) and small trial sample size (random error) may induce imprecise and exaggerated treatment effects in randomised controlled trials (RCTs). To avoid this, SPIRIT- and CONSORT-guidelines, and Cochrane Collaboration bias recommendations were developed. We investigated risk of bias and trial sample size development over time in postoperative pain trials. METHODS: This study was based on data from two systematic reviews regarding pain management after total hip arthroplasty (THA) or total knee arthroplasty (TKA). RCTs of analgesic interventions with a comparator control group were included. Primary outcomes were risk of bias and trial sample size developments over time. We calculated cumulated bias scores ranging from 0 to 14 based on Cochrane's seven bias domains (0 = low; 1 = unclear, 2 = high). Developments were evaluated with run and control charts. Further, we compared data from trials published between 1990-1999 and 2010-2016. RESULTS: We included 171 trials published between 1989 and 2016. Overall, the summarised risk of bias decreased, mainly due to better randomization and allocation concealment. Visual inspection suggested an on-going improvement that started around 2007. Trial sample size did not change significantly. For trials published between 1990-1999 and 2010-2016 adequate reporting increased from 36% to 75% for random sequence generation, from 9% to 38% for allocation concealment and from 27% to 52% for blinding of participants/personnel. CONCLUSION: Risk of bias for RCTs regarding postoperative pain management after THA and TKA has decreased from 2007 to 2016, mainly due to better randomization and allocation concealment. Deficiencies remain. Thus, reporting according to validated guidelines is essential. Sample sizes did not change significantly.

Benefit and harm of pregabalin in acute pain treatment: a systematic review with meta-analyses and trial sequential analyses.

Pregabalin has demonstrated anti-hyperalgesic properties and was introduced into acute pain treatment in 2001. Our aim was to evaluate the beneficial and harmful effects of pregabalin in postoperative pain management. We included randomized clinical trials investigating perioperative pregabalin treatment in adult surgical patients. The review followed Cochrane methodology, including Grading of Recommendations Assessment, Development, and Evaluation (GRADE), and used trial sequential analyses (TSAs). The primary outcomes were 24 h morphine i.v. consumption and the incidence of serious adverse events (SAEs) defined by International Conference of Harmonisation Good Clinical Practice guidelines. Conclusions were based primarily on trials with low risk of bias. Ninety-seven randomized clinical trials with 7201 patients were included. The 24 h morphine i.v. consumption was reported in 11 trials with overall low risk of bias, finding a reduction of 5.8 mg (3.2, 8.5; TSA adjusted confidence interval: 3.2, 8.5). Incidence of SAEs was reported in 21 trials, with 55 SAEs reported in 12 of these trials, and 22 SAEs reported in 10 trials with overall low risk of bias. In trials with overall low risk of bias, Peto's odds ratio was 2.9 (1.2, 6.8; TSA adjusted confidence interval: 0.1, 97.1). Based on trials with low risk of bias, pregabalin may have a minimal opioid-sparing effect, but the risk of SAEs seems increased. However, the GRADE-rated evaluations showed only moderate to very low quality of evidence. Consequently, a routine use of pregabalin for postoperative pain treatment cannot be recommended.

Low degree of satisfactory individual pain relief in post-operative pain trials.

BACKGROUND: The majority of clinical trials regarding post-operative pain treatment focuses on the average analgesic efficacy, rather than on efficacy in individual patients. It has been argued, that in acute pain trials, the underlying distributions are often skewed, which makes the average unfit as the only way to measure efficacy. Consequently, dichotomised, individual responder analyses using a predefined 'favourable' response, e.g. Visual Analogue Scale (VAS) pain scores ≤ 30, have recently been suggested as a more clinical relevant outcome. METHODS: We re-analysed data from 16 randomised controlled trials of post-operative pain treatment and from meta-analyses of a systematic review regarding hip arthroplasty. The predefined success criterion was that at least 80% of patients in active treatment groups should obtain VAS < 30 at 6 and 24 h post-operatively. RESULTS: In the analysis of data from the randomised controlled trials, we found that at 6 h post-operatively, 50% (95% CI: 31-69) of patients allocated to active treatment reached the success criterion for pain at rest and 14% (95% CI: 5-34) for pain during mobilisation. At 24 h post-operatively, 60% (95% CI: 38-78) of patients allocated to active treatment reached the success criterion for pain at rest, and 15% (95% CI: 5-36) for pain during mobilisation. Similar results were found for trials from the meta-analyses. CONCLUSION: Our results indicate that for conventional, explanatory trials of post-operative pain, individual patient's achievement of a favourable response to analgesic treatment is rather low. Future pragmatic clinical trials should focus on both average pain levels and individual responder analyses in order to promote effective pain treatment at the individually patient level.

Does dexamethasone have a perineural mechanism of action? A paired, blinded, randomized, controlled study in healthy volunteers.

BACKGROUND: Dexamethasone prolongs block duration. Whether this is achieved via a peripheral or a central mechanism of action is unknown. We hypothesized that perineural dexamethasone added as an adjuvant to ropivacaine prolongs block duration compared with ropivacaine alone, by a locally mediated effect when controlled for a systemic action. METHODS: We performed a paired, blinded, randomized trial, including healthy men. All subjects received bilateral blocks of the saphenous nerve with ropivacaine 0.5%, 20 ml mixed with dexamethasone 2 mg in one leg and saline in the other, according to randomization. The primary outcome was the duration of sensory block assessed by temperature discrimination in the saphenous nerve distribution. Secondary outcomes were sensory block assessed by mechanical discrimination, pain response to tonic heat stimulation, and warmth and heat pain detection thresholds. RESULTS: We included 20 subjects; one had a failed block and was excluded from the paired analysis. Block duration was not statistically significantly longer in the leg receiving dexamethasone when assessed by temperature discrimination (primary outcome, estimated median difference 1.5 h, 95% confidence interval -3.5 to 0, P=0.050). For all other outcomes, the duration was statistically significantly longer in the leg receiving dexamethasone, but the median differences were <2.0 h. Individual subject analysis revealed that only eight subjects had a block prolongation of at least 2 h in the leg receiving dexamethasone perineurally. CONCLUSION: Perineural administration of dexamethasone 2 mg showed a modest and inconsistent effect of questionable clinical relevance on block duration. CLINICAL TRIAL REGISTRATION: NCT01981746.

Post-operative serious adverse events in a mixed surgical population - a retrospective register study.

BACKGROUND: The number of surgical procedures is increasing, and knowledge of surgical risk factors, post-operative mortality and serious adverse events (SAE) is essential. The aim with our study was to determine the risk of a composite outcome of post-operative: death; myocardial infarction; pulmonary embolism; stroke; gastrointestinal bleeding; dialysis or reoperation. METHODS: Data of surgical procedures in the period from January 1, 2012 to June 30, 2012 were retrieved from the Danish Anaesthesia Database (DAD). Follow-up of all patients undergoing hip or knee replacement, abdominal or gynaecological surgery was conducted retrieving data from The Danish Civil Registration System and the National Patient Register. Total observation time was from January 1, 2012 to June 6, 2013. RESULTS: A total7449 adult patients were included in the final analysis. The risk of the composite outcome during a follow-up until 342 days after inclusion of the last patient was estimated to 8.3%, 95% Confidence Intervals (CI) (7.8-9.0), with a median observation time of 437 days (IQR 387-485, range 0-522). The risk of the composite outcome within 90- and 180-day follow-up of each patient was 4.8% (4.4-5.3) and 5.9% (5.4-6.5), respectively. Mortality within longest follow-up as well as 90 and 180 days post-operatively was 3.6% (3.1-4.0), 1.7% (1.4-2.0), and 2.2% (1.9-2.6), respectively. CONCLUSION: We found a risk of one or more events in the composite outcome within 342 days after inclusion of the last patients of 8.3% (7.8-9.0). The results are applicable in estimations of adequate sample sizes in future clinical trials investigating effects of interventions on SAEs.

Lateral femoral cutaneous nerve block after total hip arthroplasty: a randomised trial.

BACKGROUND: Peripheral regional nerve blocks are commonly used for pain management after lower extremity surgery, but motor blockade can be a significant concern. The lateral femoral cutaneous nerve (LFCN) is a purely sensory nerve from the lumbar plexus. We hypothesised that an LFCN block would reduce movement-related pain after total hip arthroplasty (THA) in patients with moderate-to-severe pain. METHODS: Sixty patients with visual analogue scale (VAS) score > 40 mm during 30-degree active flexion of the hip on either the first or second postoperative day after THA were included in this prospective, randomised, blinded, placebo-controlled trial. Group A received an LFCN block with 8 ml of 0.75% ropivacaine followed after 45 min by an additional LFCN block with 8 ml of saline. Group B received an LFCN block with 8 ml of saline followed after 45 min by an additional LFCN block with 8 ml of 0.75% ropivacaine. RESULTS: We found a difference of 17 mm (95% CI, 4-31 mm; P < 0.02) in VAS pain score during 30-degree flexion of the hip 45 min after the first block (primary outcome) in favour of group A. No other significant difference between groups regarding pain during mobilisation and at rest was found. The overall non-responder rate (< 15 mm pain reduction) was 42%. CONCLUSIONS: LFCN block reduced movement-related pain in patients with moderate-to-severe pain after THA. The substantial non-responder rate limits recommendations of this block as part of a standard analgesic treatment regimen.

Gabapentin for post-operative pain management - a systematic review with meta-analyses and trial sequential analyses.

BACKGROUND: Perioperative pain treatment often consist of combinations of non-opioid and opioid analgesics, 'multimodal analgesia', in which gabapentin is currently used. The aim was to document beneficial and harmful effects of perioperative gabapentin treatment. METHODS: Randomized clinical trials comparing gabapentin vs. placebo or active placebo in adult surgical patients receiving gabapentin perioperatively were included. This review was conducted using Cochrane standards, trial sequential analysis (TSA), and Grading of Recommendations Assessment, Development, and Evaluation (GRADE). The primary outcomes were 24-h opioid consumption and incidence of serious adverse events (SAE). RESULTS: One hundred and thirty-two trials with 9498 patients were included. Thirteen trials with low risk of bias reported a reduction in 24-h opioid consumption of 3.1 mg [0.5, 5.6] [corrected]. In the analysis of gabapentin as add-on analgesic to another non-opioid analgesic regimen found a mean reduction in 24-h morphine consumption of 1.2 mg [-0.3, 2.6; TSA-adjusted CI: -0.3, 2.6] in trials with low risk of bias. [corrected]. Nine trials with low risk of bias reported a risk ratio of SAEs of 1.61 [0.91; 2.86; TSA-adjusted CI: 0.57, 4.57]. CONCLUSION: Based on GRADE assessment of the primary outcomes in trials with low risk of bias, the results are low or very low quality of evidence due to imprecision, inconsistency, and in some outcomes indirectness. Firm evidence for use of gabapentin is lacking as clinically relevant beneficial effect of gabapentin may be absent and harm is imminent, especially when added to multimodal analgesia.

The effect of chlorzoxazone on acute pain after spine surgery. A randomized, blinded trial.

BACKGROUND: Chlorzoxazone is a muscle relaxant administered for musculoskeletal pain, and as an analgesic adjunct for post-operative pain. Chlorzoxazone for low back pain is currently not advised due to the lack of placebo-controlled trials. We explored the effect of chlorzoxazone on acute pain after spine surgery. METHODS: One hundred and ten patients were randomly assigned to 500 mg oral chlorzoxazone or placebo in this blinded study of patients having spine surgery under general anaesthesia. In the 4 h trial period analgesia consisted of IV patient-controlled analgesia (morphine bolus 2.5 mg). Primary outcome was pain during mobilization (visual analogue scale) 2 h after the intervention. Secondary outcomes were pain at rest, opioid consumption, nausea, vomiting, sedation and dizziness. RESULTS: For pain during mobilization 2 h after intervention, there was no significant difference between groups: 51 (21) vs. 54 (25) mm in the chlorzoxazone and placebo groups, respectively, mean difference 3 mm (95% CI -8 to 10), P = 0.59. For pain during mobilization and at rest (wAUC 1-4 h), there were no significant differences between groups. There was no significant difference in total IV morphine use 0-4 h: median 10 (7-21) vs. 13 (5-19) mg in the chlorzoxazone and placebo groups, respectively, P = 0.82. We found no significant difference in adverse effects. CONCLUSION: No analgesic effect of single-dose chlorzoxazone was demonstrated in patients with acute pain after spine surgery. Based on these findings, chlorzoxazone cannot be recommended for immediate treatment of acute pain after such procedures.

Effect of a high-dose target-controlled naloxone infusion on pain and hyperalgesia in patients following groin hernia repair: study protocol for a randomized controlled trial.

BACKGROUND: Central sensitization is modulated by the endogenous opioid system and plays a major role in the development and maintenance of pain. Recent animal studies performed following resolution of inflammatory pain showed reinstatement of tactile hypersensitivity induced by administration of a mu-opioid-antagonist, suggesting latent sensitization is mediated by endogenous opioids. In a recent crossover study in healthy volunteers, following resolution of a first-degree burn, 4 out of 12 volunteers developed large secondary areas of hyperalgesia areas after a naloxone infusion, while no volunteer developed significant secondary hyperalgesia after the placebo infusion. In order to consistently demonstrate latent sensitization in humans, a pain model inducing deep tissue inflammation, as used in animal studies, might be necessary. The aim of the present study is to examine whether a high-dose target-controlled naloxone infusion can reinstate pain and hyperalgesia following recovery from open groin hernia repair and thus consistently demonstrate opioid-mediated latent sensitization in humans. METHODS/DESIGN: Patients submitted to unilateral, primary, open groin hernia repair will be included in this randomized, placebo-controlled, double-blind, crossover study. The experimental days take place 6-8 weeks after surgery, time-points at which patients are expected to be almost pain- free. Prior to administration of naloxone or placebo, the primary outcome (a summated measure of pain: at rest, during transition from supine to standing position, and evoked by pressure algometry) and the secondary outcomes (secondary hyperalgesia/allodynia, pressure pain thresholds, assessed at the surgical site and at the mirror-site in the contralateral groin, and, opioid withdrawal symptoms) will be assessed. These assessments will be repeated at each step of the target-controlled infusion of placebo or naloxone at estimated median (95 % CI) plasma concentrations of 344 ng/ml (130;567), 1059 ng/ml (400;1752) and 3196 ng/ml (1205;5276). DISCUSSION: We aim to demonstrate opioid-mediated latent sensitization in a post-surgical setting, using pain as a clinical relevant variable. Impairment of the protective endogenous opioid system may play an important role in the transition from acute to chronic pain. In order to sufficiently block the endogenous opioid system, a high-dose target-controlled naloxone-infusion is used, in accordance with recent findings in animal studies. EUDRACT: 2015-000793-36 (Registration date: 16 February 2015) Clinicaltrials.gov: NCT01992146 (Registration date: 12 December 2014).

Optimal volume of local anaesthetic for adductor canal block: using the continual reassessment method to estimate ED95.

BACKGROUND: Theoretically, the ideal volume of local anaesthetic for adductor canal block (ACB) would ensure sufficient filling of the canal and avoid proximal spread to the femoral triangle. In this dose-finding study, we aimed to investigate the minimal effective volume for an ACB needed to fill the adductor canal distally in at least 95% of patients (ED95). METHODS: We performed a blinded trial, enrolling 40 healthy men. All subjects received an ACB with lidocaine 1%. Volumes were assigned sequentially to the subjects using the continual reassessment method followed by Bayesian analysis to determine the ED95. Distal filling of the adductor canal was assessed by magnetic resonance imaging (primary outcome). Secondary outcomes were the effect of volume on proximal spread to the femoral triangle (also assessed by magnetic resonance imaging), quadriceps muscle weakness (decrease by ≥25% from baseline) and sensory block. RESULTS: The ED95 was 20 ml, with an estimated probability of sufficiently filling the canal of 95.1% (95% credibility interval: 0.91-0.98). Proximal spread to the femoral triangle was seen in 0/4 (0%), 7/12 (58%), 4/8 (50%), and 8/16 (50%) subjects with the 5, 10, 15, and 20 ml doses, respectively (P=0.25). Seven subjects had a reduction in muscle strength, but there was no difference between groups (P=0.85). CONCLUSIONS: For an ACB, the dose closest to the ED95 needed to fill the adductor canal distally was 20 ml. There was no significant correlation between volume and proximal spread or muscle strength. CLINICAL TRIAL REGISTRATION: NCT02033356.

Associations between psychological variables and pain in experimental pain models. A systematic review.

BACKGROUND: The association between pain and psychological characteristics has been widely debated. Thus, it remains unclear whether an individual's psychological profile influences a particular pain experience, or if previous pain experience contributes to a certain psychological profile. Translational studies performed in healthy volunteers may provide knowledge concerning psychological factors in healthy individuals as well as basic pain physiology. The aim of this review was to investigate whether psychological vulnerability or specific psychological variables in healthy volunteers are predictive of the level of pain following experimental pain models. METHODS: A systematic search on the databases, PubMed, Embase, Cochcrane library, and Clinicaltrials.gov was performed during September 2014. All trials investigating the association between psychological variables and experimental pain in healthy volunteers were considered for inclusion. RESULTS: Twenty-nine trials met the inclusion criteria, with a total of 2637 healthy volunteers. The included trials investigated a total of 45 different psychological tests and 27 different types of pain models. The retrieved trials did not present a sufficiently homogenous group to perform meta-analysis. The collected results were diverse. A total of 16 trials suggested that psychological factors may predict the level of pain, seven studies found divergent results, and six studies found no significant association between psychological variables and experimental pain. CONCLUSION: Psychological factors may have predictive value when investigating experimental pain. However, due to substantial heterogeneity and methodological shortcomings of the published literature, firm conclusions are not possible.

Transversus abdominis plane (TAP) block after robot-assisted laparoscopic hysterectomy: a randomised clinical trial.

BACKGROUND: Transversus abdominis plane (TAP) block is widely used as a part of pain management after various abdominal surgeries. We evaluated the effect of TAP block as an add-on to the routine analgesic regimen in patients undergoing robot-assisted laparoscopic hysterectomy. METHODS: In a prospective blinded study, 70 patients scheduled for elective robot-assisted laparoscopic hysterectomy were randomised to receive either TAP block (ropivacaine 0.5%, 20 ml on each side) or sham block (isotonic saline 0.9%, 20 ml on each side). All patients had patient-controlled analgesia (PCA) with morphine on top of paracetamol and ibuprofen or diclofenac. For the first 24 post-operative hours, we monitored PCA morphine consumption and pain scores with visual analogue scale (VAS) at rest and while coughing. Post-operative nausea and number of vomits (PONV) were recorded. RESULTS: Sixty-five patients completed the study, 34 receiving TAP block with ropivacaine and 31 receiving sham block with isotonic saline. We found no differences in median (interquartile range) morphine consumption the first 24 h between the TAP block group [17.5 mg (6.9-36.0 mg)] and the placebo group [17.5 mg (2.9-38.0 mg)] (95% confidence interval 10.0-22.6 mg, P = 0.648). No differences were found for VAS scores between the two groups, calculated as area under the curve/1-24 h, neither at rest (P = 0.112) nor while coughing (P = 0.345), or for PONV between groups. CONCLUSIONS: In our study, the TAP block combined with paracetamol and Nonsteroidal anti-inflammatory drugs (NSAID) treatment, had no effect on morphine consumption, VAS pain scores, or frequency of nausea and vomiting after robot-assisted laparoscopic hysterectomy compared with paracetamol and NSAID alone.

Adductor canal blockade for moderate to severe pain after arthroscopic knee surgery: a randomized controlled trial.

BACKGROUND: The analgesic effect of the adductor canal block (ACB) after knee surgery has been evaluated in a number of trials. We hypothesized that the ACB would provide substantial pain relief to patients responding with moderate to severe pain after arthroscopic knee surgery. METHODS: Fifty subjects with moderate to severe pain after arthroscopic knee surgery were enrolled in this placebo-controlled, blinded trial. All subjects received two ACBs; an initial ACB with either 30 ml ropivacaine 7.5 mg/ml (n = 25) (R group) or saline (n = 25) (C group) and after 45 min a second ACB with the opposite study medication, according to randomization. Primary outcome was pain during 45 degrees active flexion of the knee at 45 min after the first block, assessed on a 0-100 mm visual analogue scale. Secondary outcome measures were: pain at rest and during flexion of the knee, worst pain experienced during a 5-m walk, patient's evaluation of muscle strength during walk, and amount of sufentanil administered during the 90-min study period. RESULTS: Regarding primary outcome, mean pain score difference between groups was 34 (95% CI: 25 to 44) mm, P < 0.001, in favour of the R group. At rest, mean pain score difference was 32 (23 to 41) mm, P < 0.001, and during walk: 21 (6 to 36) mm, P = 0.01 in favour of the R group. There were no differences between groups regarding other secondary outcome measures. CONCLUSION: The ACB is a relevant option for patients with moderate to severe pain after arthroscopic knee surgery.

Adverse effects of perioperative paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations: a topical review.

Post-operative pain affects millions of patients worldwide and the post-operative period has high rates of morbidity and mortality. Some of this morbidity may be related to analgesics. The aim of this review was to provide an update of current knowledge of adverse events (AE) associated with the most common perioperative non-opioid analgesics: paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (GCCs), gabapentinoids and their combinations. The review is based on data from systematic reviews with meta-analyses of analgesic efficacy and/or adverse effects of perioperative non-opioid analgesics, and randomised trials and cohort/retrospective studies. Generally, data on AE are sparse and related to the immediate post-operative period. For paracetamol, the incidence of AEs appears trivial. Data are inconclusive regarding an association of NSAIDs with mortality, cardiovascular events, surgical bleeding and renal impairment. Anastomotic leakage may be associated with NSAID usage. No firm evidence exists for an association of NSAIDs with impaired bone healing. Single-dose GCCs were not significantly related to increased infection rates or delayed wound healing. Gabapentinoid treatment was associated with increased sedation, dizziness and visual disturbances, but the clinical relevance needs clarification. Importantly, data on AEs of combinations of the above analgesics are sparse and inconclusive. Despite the potential adverse events associated with the most commonly applied non-opioid analgesics, including their combinations, reporting of such events is sparse and confined to the immediate perioperative period. Knowledge of benefit and harm related to multimodal pain treatment is deficient and needs clarification in large trials with prolonged observation.

Post-operative analgesic effects of paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations: a topical review.

In contemporary post-operative pain management, patients are most often treated with combinations of non-opioid analgesics, to enhance pain relief and to reduce opioid requirements and opioid-related adverse effects. A diversity of combinations is currently employed in clinical practice, and no well-documented 'gold standards' exist. The aim of the present topical, narrative review is to provide an update of the evidence for post-operative analgesic efficacy with the most commonly used, systemic non-opioid drugs, paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs)/COX-2 antagonists, glucocorticoids, gabapentinoids, and combinations of these. The review is based on data from previous systematic reviews with meta-analyses, investigating effects of non-opioid analgesics on pain, opioid-requirements, and opioid-related adverse effects. Paracetamol, NSAIDs, COX-2 antagonists, and gabapentin reduced 24 h post-operative morphine requirements with 6.3 (95% confidence interval: 3.7 to 9.0) mg, 10.2 (8.7, 11.7) mg, 10.9 (9.1, 12.8) mg, and ≥ 13 mg, respectively, when administered as monotherapy. The opioid-sparing effect of glucocorticoids was less convincing, 2.33 (0.26, 4.39) mg morphine/24 h. Trials of pregabalin > 300 mg/day indicated a morphine-sparing effect of 13.4 (4, 22.8) mg morphine/24 h. Notably, though, the available evidence for additive or synergistic effects of most combination regimens was sparse or lacking. Paracetamol, NSAIDs, selective COX-2 antagonists, and gabapentin all seem to have well-documented, clinically relevant analgesic properties. The analgesic effects of glucocorticoids and pregabalin await further clarification. Combination regimens are sparsely documented and should be further investigated in future studies.

The analgesic effect of wound infiltration with local anaesthetics after breast surgery: a qualitative systematic review.

BACKGROUND: Wound infiltration with local anaesthetics is commonly used during breast surgery in an attempt to reduce post-operative pain and opioid consumption. The aim of this review was to evaluate the effect of wound infiltration with local anaesthetics compared with a control group on post-operative pain after breast surgery. METHODS: A systematic review was performed by searching PubMed, Google Scholar, the Cochrane database and Embase for randomised, blinded, controlled trials of wound infiltration with local anaesthetics for post-operative pain relief in female adults undergoing breast surgery. The analgesic effect was evaluated in a qualitative analysis by assessment of significant difference between groups (P < 0.05) in pain scores and supplemental analgesic consumption. RESULTS: Ten trials including 699 patients were included in the final analysis. Three trials investigated mastectomy, four trials partial or segmental mastectomy, and three trials breast reduction, excision of benign lump and unspecified breast surgery, respectively. Six trials demonstrated a small and short-lasting, but statistically significant reduction of post-operative pain scores, and four trials observed a statistically significant reduction in post-operative, supplemental opioid consumption that was, however, of limited clinical relevance. CONCLUSION: Wound infiltration with local anaesthetics may have a modest analgesic effect in the first few hours after surgery. Pain after breast surgery is, however, generally mild to moderate, and other non-invasive analgesic methods may be preferable in this surgical population.

Effect of adductor canal block on pain in patients with severe pain after total knee arthroplasty: a randomized study with individual patient analysis.

BACKGROUND: Total knee arthroplasty (TKA) is associated with varying degrees of pain. A considerable proportion (25-40%) of patients experience severe pain, despite a comprehensive multimodal analgesic regimen. We hypothesized that adductor canal block (ACB) would reduce pain in this patient category compared with placebo. METHODS: Fifty patients with severe pain, defined as having a visual analogue scale (VAS) pain score of >60 during active flexion of the knee on the first or the second postoperative day after TKA, were included in this randomized, double-blind, placebo-controlled trial. All the patients had received a comprehensive multimodal analgesic regimen. Group A received an ACB with ropivacaine 0.75%, 30 ml at time 0 and isotonic saline after 45 min. Group B received an ACB with isotonic saline at time 0 and ropivacaine 0.75%, 30 ml after 45 min. RESULTS: A 32-mm difference in VAS pain score, during active flexion of the knee (primary endpoint), was observed in favour of Group A, 95% confidence interval (CI): 23-42, P<0.0001. At rest, the difference in VAS pain score was 15 mm in favour of Group A, 95% CI: 8-23 mm, P=0.0001. Individual patient analysis revealed that 25% of the patients had no effect during active flexion. At rest, however, only 8% had more than mild pain after ACB compared with 57% at inclusion. CONCLUSIONS: ACB reduced VAS with 32 mm, during active flexion of the knee, in patients with severe pain after TKA, but a large proportion (78%) still had at least moderate, movement-related pain. Clinical trial registration www.clinicaltrials.gov, NCT01549704.