The efficacy and safety of ankle blocks for foot and ankle surgery: A systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: Peripheral nerve blocks may be essential elements in a multimodal pain management regime following foot and ankle surgery. We assessed the effects of ankle blocks compared with no intervention/sham block or a sciatic nerve block in patients undergoing surgery of the foot or ankle. METHODS: We searched CENTRAL, Medline, and Embase for randomised clinical trials comparing ankle block with no intervention/sham block or a sciatic nerve block for patients undergoing surgery of the foot or ankle. Our primary outcomes were duration of analgesia and cumulative 24-hour opioid consumption. We followed the recommendations of the Cochrane Handbook, and performed meta-analysis, Trial Sequential Analysis (TSA), and assessed the risk of bias and certainty of the evidence using the GRADE approach. RESULTS: We included five trials (362 participants) comparing ankle block with no intervention/sham block and three trials (247 participants) comparing ankle block with a sciatic nerve block. Ankle block may increase the duration of analgesia when compared with no intervention/sham block (MD 431 min; 96.7% CI 208 to 654), but the evidence was very uncertain. Duration was decreased when compared with a sciatic nerve block (MD -410 min; 96.7% CI -462 to -358). The ankle block duration was probably important in both comparisons. The effects on cumulative 24-hour opioid consumption were very uncertain in both comparisons. CONCLUSIONS: Ankle block may increase the duration of analgesia when compared with no intervention/sham block, but the evidence was very uncertain, and decrease the duration of analgesia when compared with a sciatic nerve block. The ankle block duration was probably clinically important in both comparisons. The effects on cumulative 24-hour opioid consumption were very uncertain.

Combined Dexamethasone and Dexmedetomidine as Adjuncts to Popliteal and Saphenous Nerve Blocks in Patients Undergoing Surgery of the Foot or Ankle: A Randomized, Blinded, Placebo-controlled Clinical Trial.

BACKGROUND: Both dexamethasone and dexmedetomidine increase the duration of analgesia of peripheral nerve blocks. The authors hypothesized that combined intravenous dexamethasone and intravenous dexmedetomidine would result in a greater duration of analgesia when compared with intravenous dexamethasone alone and placebo. METHODS: The authors randomly allocated participants undergoing surgery of the foot or ankle under general anesthesia and with a combined popliteal (sciatic) and saphenous nerve block to a combination of 12 mg dexamethasone and 1 µg/kg dexmedetomidine, 12 mg dexamethasone, or placebo (saline). The primary outcome was the duration of analgesia measured as the time from block performance until the first sensation of pain in the surgical area as reported by the participant. The authors predefined a 33% difference in the duration of analgesia as clinically relevant. RESULTS: A total of 120 participants from two centers were randomized and 119 analyzed for the primary outcome. The median [interquartile range] duration of analgesia was 1,572 min [1,259 to 1,715] with combined dexamethasone and dexmedetomidine, 1,400 min [1,133 to 1,750] with dexamethasone alone, and 870 min [748 to 1,138] with placebo. Compared with placebo, the duration was greater with combined dexamethasone and dexmedetomidine (difference, 564 min; 98.33% CI, 301 to 794; P < 0.001) and with dexamethasone (difference, 489 min; 98.33% CI, 265 to 706; P < 0.001). The prolongations exceeded the authors' predefined clinically relevant difference. The duration was similar when combined dexamethasone and dexmedetomidine was compared with dexamethasone alone (difference, 61 min; 98.33% CI, -222 to 331; P = 0.614). CONCLUSIONS: Dexamethasone with or without dexmedetomidine increased the duration of analgesia in patients undergoing surgery of the foot or ankle with a popliteal (sciatic) and saphenous nerve block. Combined dexamethasone and dexmedetomidine did not increase the duration of analgesia when compared with dexamethasone.

Perineural and Systemic Dexamethasone and Ulnar Nerve Block Duration: A Randomized, Blinded, Placebo-controlled Trial in Healthy Volunteers.

BACKGROUND: The authors hypothesized that both perineural and systemic dexamethasone as adjuncts to bupivacaine increase the duration of an ulnar nerve block compared with bupivacaine alone, and that systemic dexamethasone is noninferior to perineural dexamethasone. METHODS: The authors performed bilateral ulnar nerve blocks with 3 ml bupivacaine 5 mg/ml in 16 healthy volunteers on two trial days. According to randomization, subjects received adjunct treatment with 1 ml dexamethasone 4 mg/ml + 1 ml of saline (perineural condition) in one arm and 2 ml saline in the other arm (systemic condition, through absorption and redistribution of the contralaterally administered perineural dexamethasone) on one trial day; and 2 ml saline in one arm (placebo condition) and 2 ml of lidocaine in the other arm (lidocaine condition) on the other trial day. The primary outcome was the duration of the sensory nerve block assessed by temperature discrimination. RESULTS: Mean sensory block duration was 706 ± 94 min for the perineural condition, 677 ± 112 min for the systemic condition, and 640 ± 121 min for the placebo condition. The duration of the sensory nerve block was greater with perineural dexamethasone versus placebo (mean difference 66 min (95% CI, 23 to 108). Block duration was similar between systemic dexamethasone and placebo (mean difference 36 min; 95% CI, -30 to 103). CONCLUSIONS: Perineural dexamethasone as an adjunct to bupivacaine in healthy volunteers resulted in a greater duration of an ulnar nerve block when compared with placebo. Systemic dexamethasone resulted in a similar duration as placebo.

Systemic glucocorticoids as an adjunct to treatment of postoperative pain after total hip and knee arthroplasty: A systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: Postoperative analgesic effects of systemic glucocorticoids given as an adjunct to treatment are largely undetermined in alloplastic procedures. OBJECTIVES: To investigate the beneficial and harmful effects of peri-operative systemic glucocorticoid treatment for pain after total hip arthroplasty (THA) or total knee arthroplasty (TKA). DESIGN: A systematic review of randomised clinical trials (RCTs) with meta-analyses, trial sequential analyses and GRADE. Primary outcome was 24 h intravenous (i.v.) morphine (or equivalent) consumption with a predefined minimal important difference (MID) of 5 mg. Secondary outcomes included pain at rest and during mobilisation (MID, VAS 10 mm), adverse and serious adverse events (SAEs). DATA SOURCES: We searched EMBASE, Cochrane CENTRAL, PubMed and Google Scholar up to October 2021. ELIGIBILITY CRITERIA: RCTs investigating peri-operative systemic glucocorticoid versus placebo or no intervention, for analgesic pain management of patients at least 18 years undergoing planned THA or TKA, irrespective of publication date and language. RESULTS: We included 32 RCTs with 3521 patients. Nine trials were at a low risk of bias. Meta-analyses showed evidence of a reduction in 24 h cumulative morphine consumption with glucocorticoids by 5.0 mg (95% CI 2.2 to 7.7; P  = 0.0004). Pain at rest was reduced at 6 h by 7.8 mm (95% CI 5.5 to 10.2; P  < 0.00001), and at 24 h by 6.3 mm (95% CI 3.8 to 8.8; P  < 0.00001). Pain during mobilisation was reduced at 6 h by 9.8 mm (95% CI 6.9 to 12.8; P  < 0.00001), and at 24 h by 9.0 mm (95% CI 5.5 to 12.4, P  < 0.00001). Incidence of adverse events was generally lower in the glucocorticoid treatment group. SAEs were rarely reported. The GRADE rated quality of evidence was low to very low. CONCLUSION: Peri-operative systemic glucocorticoid treatment reduced postoperative morphine consumption to an individually relevant level following hip and knee arthroplasty. Pain levels were reduced but were below the predefined MID. The quality of evidence was generally low. REGISTRATION: PROSPERO ID: CRD42019135034.

Alpha2 -receptor agonists as adjuvants for brachial plexus nerve blocks-A systematic review with meta-analyses.

BACKGROUND: We review the efficacy and safety of dexmedetomidine and clonidine as perineural or systemic adjuvants for brachial plexus blocks (BPB). METHODS: We included randomised controlled trials on upper limb surgery with BPBs in adults, comparing dexmedetomidine with clonidine or either drug with placebo. The primary outcome was duration of analgesia. Secondary outcomes included adverse and serious adverse events. The review was conducted using Cochrane standards, trial sequential analyses (TSA) and Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: We included 101 trials with 6248 patients. Overall, duration of analgesia was prolonged with both clonidine (176 min [TSA adj. 95% CI: 118, 205, p < .00001; 33 trials]) and dexmedetomidine (292 min [TSA adj. 95% CI: 245 329, p < .00001; 53 trials]), but was longer for dexmedetomidine than clonidine (205 min [TSA adj. 95% CI: 157, 254, p < .00001; 19 trials]). Compared with placebo, dexmedetomidine was associated with bradycardia (RR 4.2 [95% CI 2.2, 8.3]), and both clonidine (RR 4.5 [95% CI 1.1, 18.3]) and dexmedetomidine (RR 3.9 [95% CI 2.0, 7.5]) were associated with hypotension. Serious adverse events were mostly related to block technique. GRADE-rated quality of evidence was low or very low. CONCLUSION: Alpha2-receptor agonists used as adjuvants for BPBs lead to a prolonged duration of analgesia, with dexmedetomidine as the most efficient. Alpha2-receptor agonists were associated with increased risk of cardiovascular adverse events. The quality of evidence was low to very low.

Does Dexmedetomidine Have a Perineural Mechanism of Action When Used as an Adjuvant to Ropivacaine?: A Paired, Blinded, Randomized Trial in Healthy Volunteers.

BACKGROUND: Dexmedetomidine used as an adjuvant to local anesthetics may prolong the duration of peripheral nerve blocks. Whether this is mediated by a perineural or systemic mechanism remains unknown. The authors hypothesized that dexmedetomidine has a peripheral mechanism of action. METHODS: The authors conducted a randomized, paired, triple-blind trial in healthy volunteers. All received bilateral saphenous nerve blocks with 20 ml ropivacaine, 0.5%, plus 1 ml dexmedetomidine, 100 µg/ml, in one thigh and 20 ml ropivacaine 0.5% plus 1 ml saline in the other thigh. The primary outcome measure was the duration of block assessed by temperature sensation (alcohol swab). The secondary outcome measure was the duration of block assessed by pinprick, pain during tonic heat stimulation, warmth detection threshold, and heat pain detection threshold. RESULTS: All 21 enrolled volunteers completed the trial. The mean duration of block assessed by temperature sensation in the leg receiving ropivacaine plus dexmedetomidine was 22 h (95% CI, 21 to 24) compared to 20 h (95% CI, 19 to 21) in the leg receiving ropivacaine plus placebo with a mean difference of 2 h (95% CI, 1 to 3; P = 0.001). The duration of block was also significantly longer in the leg receiving dexmedetomidine when assessed by pinprick, pain during tonic heat stimulation, and warmth detection threshold but not heat pain detection threshold. One participant experienced numbness in an area in the leg receiving dexmedetomidine. CONCLUSIONS: Dexmedetomidine prolongs the duration of a saphenous nerve block by a peripheral mechanism when controlling for systemic effects but not necessarily to a clinically relevant extent.