PERINEURAL DEXAMETHASONE DR JAKE DRINKWATER; ST6 ANAESTHETICS

Transcription

1 PERINEURAL DEXAMETHASONE DR JAKE DRINKWATER; ST6 ANAESTHETICS

2 What Do We Want To Know About Perineural Dexamethasone? Does perineural Dex prolong duration of PNB? How does perineural compare to systemic Dex? What perineural dose should we use? Is it safe? What is current best practice?

3 DOES PERINEURAL DEXAMETHASONE PROLONG DURATION OF PNB?

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6 195 Patients, ACL reconstruction 13ml 0.5% Bup (control) & 1mg Dex: HR 0.48( )[P=0.001] & 4mg Dex: HR 0.52( )[P=0.004] Median block duration: 33.1, 41.2 & 46.5hrs Addition of 1 & 4 mg of Dex significantly increased SSNB duration by 8h &13 h compared to control

7 Prospective, randomised, controlled trial 40 patients, Sciatic catheter plus Sub-sartorial Saphenous Nerve Block with 10ml 0.5% But, 1: Adrenaline & either 1ml Dex (4mg) or 1ml Saline Primary outcome = Time to first opioid request Dex vs Control group: 29.4h vs 23.2h [P=0.048] Opioid consumption 0-24hrs: 0mg(0-0) vs 1.5mg(0-14.2) [P<0.05] No significant diff in opioid consumption 24-48h post-op

8 DOES PERINEURAL DEXAMETHASONE PROLONG DURATION OF PNB?.YES!

9 DOES IT MATTER WHAT ROUTE DEXAMETHASONE IS GIVEN BY?

10 Prospective, double blind, randomised, RCT Arthroscopic shoulder surgery with USG ISB Primary outcome = Time to first analgesic request Rop 0.5%: 757 min (IQR ) Rop 0.5% & Dex 10mg PN: 1405 min (IQR ) Rop 0.5% & Dex 10mg IV: 1275 min (IQR ) Significant difference between the Rop & Dex groups (P<0.0001) No significant difference between Dex groups

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12 Sciatic study: fewer PN dexamethasone group patients experienced pain at 24 hours (13% vs 47%, P = 0.01) No benefit at any time for the ankle block Pooled analysis of the 2 individual studies showed absence of significant PN dexamethasone effect: hazard ratio 0.81 ( ) P = 0.94 No differences between groups for all other study outcomes including worst and average pain, the requirement for tramadol, and patient satisfaction

13 Group 1: PN Dex 8mg/2ml & 50ml IV saline Group 2: PN Saline 2ml & 8mg Dex IV (50ml) Group 3: PN Saline 2ml & 50l Saline Primary outcome = Global score in Quality of Recovery (QoR-40) No difference in QoR-40 at 24h between groups Both Dex groups prolonged motor block vs Control Only PN Dex significantly prolonged analgesic duration vs Control No significant differences between PN and IV Dex regards motor block duration and analgesia

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15 Given the lack of clinical benefit and the concern of dexamethasone neurotoxicity as demonstrated in animal studies, the practice of perineural dexamethasone administration needs to be further evaluated

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17 A 75 patients (3 groups of 25), USG Supraclavicular BPB Primary outcome = Duration of analgesia 30ml Bup 0.5%(13.2 hours [ ]) & IV Dex 8mg (25 hours [ ];P < ) & Perineural Dex 8 mg (25 hours [ ]; P = 1) IV & Perineural Dex had pain scores, postoperative opioid consumption, and satisfaction compared with Control IV Dex similar to Perineural Dex in prolonging duration of analgesia

18 90 Patients, 3 Groups USG Ankle Block, 20ml Rop 0.75% Control: & IV saline (2ml) Perineural: with Perineural Dex 8mg & Saline IV (2ml) IV: & IV Dex 8mg (2ml) Dexamethasone prolonged time until block started to wear off & time return of normal sensation and movement Route of dexamethasone administration did not affect when the block started to wear off or finished wearing off, p = 0.27 and 0.35, respectively.

19 Paired, blinded, randomized trial; 19 patients Bilateral SSNB Rop 0.5%, 20 ml mixed with dexamethasone 2 mg in one leg and saline in the other Primary outcome = Duration of sensory block (assessed by temperature discrimination) Secondary outcomes = Sensory block (mechanical discrimination), pain response to tonic heat stimulation, and warmth & heat pain detection thresholds. Block duration not significantly longer in the leg receiving Dex: median diff 1.5h[ 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 <2.0h. Individual subject analysis revealed that 8 subjects had block prolongation >2h

20 35ml (1% Lid, 0.25% Bup, Adrenaline 5mcg/ml) Dex 5mg: PN vs IV (HOURS) PN IV Motor (P<0.009) Sensory (P<0.002) Analgesia (P<0.014) 15.7 (±6.2) 12.9 (±5.5) 16.8 (±4.4) 13.9 (±5.4) 22.1 (±8.5) 18.6 (±6.7)

21 8mg Dex with Rop in the block injection (n = 42) 8 mg Dex IV at the time of the block (n = 37) IV saline (n = 41) at the time of the block PN IV Saline Block Duration (h) 16.9 (±5.2) 18.2 (±6.4) 13.8 (±3.8) (P<0.001) Mean Opioid (mg) Consumption (0-24h) 12.2 (±9.3) 17.1 (±15.9) 24.1 (±14.3) (P<0.001)

22 Double blind, RCT; 99 Patients USG Interscalene BPB, with Fent & Midaz Sed 12ml 0.5% Rop & 1ml Dex IV (5mg) 12ml 0.5% Rop with Dex 5mg & 1ml saline IV GA (Thio, Fent, Roc) Primary outcome = Time to first analgesia request IV: 1080 min (SD 117.5) Perineural: 810 min (SD 48.1) P=0.02 No significant difference in Blood glucose (Pre and Post-op)

23 Randomised, controlled, double blind trial 150 patients (2 groups of 75), USG Axilliary BPB 1% lidocaine, 0.25% bupivacaine (30 ml) & Adrenaline 5μg/ml Preservative-free Dex 8mg: IV vs perineural Motor block 17.5(4.6)hr vs 12.8(4.5)hr [mean diff 4.6 hr;p<0.001] Sensory block 17.7(5.1)hr vs 13.7(5.0)hr [mean difference 4.0hr; P<0.001] Post-op analgesia 21.1(4.6)hr vs 17.1(4.6)hr [mean difference 4.0hr;P<0.001] Compared to intravenous dosing, perineural dexamethasone (8 mg) results in longer durations of sensorimotor block and postoperative analgesia for ultrasound-guided axillary block

24 DOES IT MATTER WHAT ROUTE DEXAMETHASONE IS GIVEN BY?

25 2mg 4mg 5mg 8mg 10mg Desmet 2013 Fredrickson 2013 Fredrickson 2013 Rahangdale 2014 Kawanishi 2014 Abdallah 2015 Dawson 2015 Jaeger 2016 Leurcharusmee 2016 Rosenfeld 2016 Chun 2016 Aliste 2017 Intercsalene Sciatic Ankle Sciatic Interscalene Supraclavicular Ankle SSNB Infraclavicular Interscalene Interscalene Axilliary

26 DOES IT MATTER WHAT ROUTE DEXAMETHASONE IS GIVEN BY??????

27 WHAT IS THE DOSE OF PERINEURAL DEXAMETHASONE?

28 90 Patients, Shoulder surgery, Interscalene Block (40ml 0.5% Bup) Perineural Dexamethasone: none vs 4mg vs 8mg None 4mg 8mg Analgesic duration (h) Motor Block (h) Analgesic Consumption (Tablets) 13.3 (±1.0) (P<0.05) 24.6 (±3.3) (P<0.05) 9.5 (8-12) (P<0.01) 21.6 (±2.4) 25.2 (±1.9) 36.7 ( ±4.1) 39.1 (±3.9) 6.5 (4-8) 5.5 (4-7)

29 The addition of dexamethasone to bupivacaine significantly prolonged the duration of the motor block and improved the quality of analgesia following interscalene block There was no difference in the duration of analgesia and motor block between low-dose and high-dose dexamethasone

30 WHAT IS THE DOSE OF PERINEURAL DEXAMETHASONE?.4MG? BUT INSUFFICIENT DATA

31 IS PERINEURAL DEXAMETHASONE SAFE?

32 Trypan blue exclusion assay used to assess death of sensory neurons isolated from adult male Sprague-Dawley rats Drugs were applied, alone or in combination, for 2 or 24 hrs at 37-C Ropivicaine, Clonidine, Buprenorphine, Midazolam, Dexamethasone.

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34 Ropivicaine is neurotoxic - Halving neuronal viability at 24hrs Ropivicaine neurotoxicity far exceeds C, B, D or M Midazolam is neuro toxic - Small but sig. increased toxicity High Conc. B, C & M increases Neurotoxicity of R R & M combo killed >90% neurons at 2hrs Clinical concentrations of C + B + Dex 66mcg/ml do not influence toxicity due to R + M R+C+B with Dex 133mcg/ml increased neurotoxic effect!

35 Didn t look at R + D 667mcg/ml for 24h, only at 2 hr Didn t look at Dexamethasone without other additives for any other concentration 667mcg/ml = 13.3mg in 20ml: No more toxic than r alone at 2hrs 66.6mcg/ml = 1.33mg in 20ml or 2mg in 30ml: No more toxic than R alone at 24hrs 133mcg/ml = 2.26mg in 20ml or 3.99mg in 30ml: more neurotoxic when combined with R+C+B vs 66.6mcg/ml of Dex

36 5 Groups: Each different perineural solution Saline, Rop, Dex, Rop & Dex, Rop & Systemic Dex Sensory & motor block evaluated every 30 mins for 14 hrs 9 mice in each group were killed (d14 & d28) for sciatic nerve histological assessment No statistical difference between groups for Wallerian degeneration (P=0.28 d14 & P=0.22 d28) No statistical difference between groups for perineural inflammation (P=0.9 d14) (Minutes) Rop Rop & Dex (PN) Rop & Dex (sys) Motor Sensory 60 (P<0.05) 330 (P<0.05)

37 IS PERINEURAL DEXAMETHASONE SAFE? INSUFFICIENT DATA

38 WHAT IS CURRENT BEST PRACTICE?

39 Best Practice? Peripheral nerve and plexus blocks, used appropriately, have analgesic and opioid sparing benefits Plain LA blocks may provide analgesia for 8-16 hrs depending upon various factors Dexamethasone by any route may significantly prolong the duration of the block

40 Best Practice? There are many studies demonstrating statistical equivalence between perineural and systemic dexamethasone administration Some studies have demonstrated a statistically significant additional prolongation of block duration with perineural compared to systemic dexamethasone One study suggested there is no statistical benefit with PN but not IV Dexamethasone Some studies have shown trends elude to a dose dependant prolongation of the block when using perineural dexamethasone, but this has not been shown to be statistically significant (4mg vs 8mg)

41 Best Practice? Increasing the perineural dose from 2mg to 4mg in 30ml increases neurotoxicity when used in combination with Ropicicaine, clonidine and buprenorphine (the effect of dexamethasone alone in these concentrations has not been studied) Certainly the LA is likely to be the most toxic component of drugs used to block nerves How closely do murine models reflect the human model? Is the additional marginal prolongation of block duration clinically significant when weighed against the possibility of neurotoxicity

42 THANK YOU