Comparison of the analgesic effect of an adductor canal block using a new suture-method catheter vs. standard perineural catheter vs. single-injection: a randomised, blinded, controlled study.

We performed a randomised, blinded, controlled study with adult patients scheduled for primary total knee arthroplasty under spinal anaesthesia. The aim was to investigate the analgesic effects of adductor canal block using catheter-based repeated boluses, either through a new suture-method catheter or a standard perineural catheter, compared with a single-injection technique. All patients received an adductor canal block after surgery with an initial bolus of 20 ml ropivacaine 0.75%, followed by 20 ml of ropivacaine 0.2% every 8 h in the standard and suture-method catheter groups, and sham boluses for the single-injection group. The primary outcome measure was total opioid consumption (intravenous morphine equivalents) from the end of surgery until 12:00 on postoperative day 2. Secondary outcomes were pain, muscle strength and ambulation. We randomly assigned (1:1:1) and analysed 153 patients. Total opioid consumption was median (IQR [range]) 24 (11-37 [0-148]) mg in the suture-method group, 38 (17-51 [0-123]) mg in the standard catheter group and 37 (14-57 [0-158]) mg in the single-injection group (p = 0.049). Differences were not statistically significant after Bonferroni correction (α = 0.05/3). There were no differences between groups on postoperative day 1. On postoperative day 2, there were no differences between catheter groups, but muscle strength and ambulation were improved compared with the single-injection group. We conclude that providing repeated boluses via a catheter did not decrease opioid consumption or pain compared with a single injection, but improved muscle strength and ambulation on postoperative day 2. The two types of catheters were similar.

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.

A randomized trial of the effect of low dose epinephrine infusion in addition to tranexamic acid on blood loss during total hip arthroplasty.

BACKGROUND: Total hip arthroplasty (THA) is associated with both intraoperative and postoperative blood loss resulting in anaemia and, in some patients, transfusion of red blood cells. Epinephrine enhances coagulation by several mechanisms. We evaluated the effect of intraoperative low dose infusion of epinephrine on intraoperative and early postoperative blood loss. METHODS: After consent, 106 subjects undergoing THA under spinal anaesthesia were randomly assigned to receive an i.v. infusion of either epinephrine 0.05 µg kg(-1) min(-1) or placebo (saline 0.9%) during the entire surgical procedure. Intraoperative tranexamic acid (TXA) was administered to all subjects. The primary outcome was intraoperative blood loss directly measured by drains and weighing swabs. Secondary outcome was total blood loss at 24 h postoperatively calculated using the Gross formula. RESULTS: Of 106 subjects randomized, 6 were excluded, leaving 100 subjects for analyses. Mean duration of surgery was 58 (21) min. Intraoperative blood loss was 343 (95% CI 300-386) ml in the epinephrine group compared with 385 (353-434) ml in the placebo group, P = 0.228. 24 h blood loss was 902 (800-1004) ml in the epinephrine group compared with 1080 (946-1220) ml in the placebo group, P = 0.038. CONCLUSION: In subjects also receiving TXA, intraoperative low dose epinephrine infusion did not reduce intraoperative blood loss in THA but calculated 24 h blood loss was reduced by 180 ml compared with placebo. Further studies on low dose epinephrine in patients at high risk of significant bleeding are warranted. CLINICAL TRIAL REGISTRATION: NCT 01708642.

Transfer of liraglutide from blood to cerebrospinal fluid is minimal in patients with type 2 diabetes.

Treatment with liraglutide leads to weight loss. We investigated whether blood-to-cerebrospinal fluid (CSF) transfer of liraglutide occurs, and if so, whether it associates with clinical weight loss following liraglutide treatment in humans. We performed lumbar puncture and blood sampling in eight patients with type 2 diabetes (mean (range)): age 63 (54-79) years; actual body weight: 90 (75-118) kg treated with 1.8 mg liraglutide for 14 (5-22) months and with a treatment-induced weight loss of 8.4 (7-11) kg. We measured liraglutide in plasma and CSF with a radioimmunoassay specific for the N-terminus of the GLP-1 moiety of liraglutide. Mean plasma liraglutide was 31 (range: 21-63) nmol l(-1). The mean CSF-liraglutide concentration was 6.5 (range: 0.9-13.9) pmol l(-1). Ratio of CSF: plasma-liraglutide concentrations was 0.02 (range: 0.07-0.002)% and plasma liraglutide did not correlate with CSF-liraglutide levels (P=0.67). Body weight loss tended to correlate with plasma-liraglutide levels (P=0.06), but not with CSF-liraglutide levels (P=0.69). In conclusion, we measured very low concentrations of liraglutide in CSF, and the levels of CSF liraglutide did not correlate with the actual clinical weight loss in these patients. The amount of liraglutide in plasma tended to correlate with the clinical weight loss.

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.

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.

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

BACKGROUND: 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. METHODS: We enrolled patients scheduled for elective TKA into this double-blind, placebo-controlled, randomised study. During general anaesthesia, we placed a catheter in the adductor canal, and after obtaining pre-block pain scores 30 min post-operatively, we injected 30 ml of ropivacaine 0.75% (n = 21) or saline (n = 20) according to randomisation. Clinicaltrials.gov Identifier: NCT01261897. RESULTS: Forty-two patients were randomised, and 41 were analysed. Mean (standard deviation) pain scores during flexion of the knee at 1 h post-operatively were 58 (22) mm and 67 (29) mm, ropivacaine and placebo group, respectively (P = 0.23) but was significantly reduced in the ropivacaine group when calculated as area under the curve for the interval 1-6 h (P = 0.02). There were no statistically significant differences regarding pain at rest (P = 0.08), morphine consumption (P = 0.06), nor morphine-related side effects, apart from nausea (P = 0.04). CONCLUSION: This proof-of-concept study shows promising results regarding the analgesic efficacy of adductor-canal-blockade in post-operative pain treatment after TKA, with a significant reduction in pain during flexion of the knee in the early post-operative period compared with placebo. However, the study was not sufficiently powered to permit final conclusions.