Comparing block characteristics of mixtures of short/intermediate- and long-acting local anesthetics for peripheral nerve block: a systematic review and meta-analysis

Lin, Cheng; Guerrero, Ana Larissa; Jesin, Joshua; Tangri, Rohin; Luginaah, Nasong Anthony; Kumar, Kamal; Hansebout, Christopher

doi:10.1016/j.bjane.2025.844617

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Review Article • Braz. J. Anesthesiol. 75 (3) • 2025 • https://doi.org/10.1016/j.bjane.2025.844617 linkcopy

Comparing block characteristics of mixtures of short/intermediate- and long-acting local anesthetics for peripheral nerve block: a systematic review and meta-analysis

Authorship SCIMAGO INSTITUTIONS RANKINGS

Introduction

Results from Randomized Controlled Trials (RCTs) on mixed Local Anesthetics (LA) are conflicting. We conducted a systematic review and meta-analysis on whether using mixed LA leads to faster onset of surgical block.

Method We conducted systemic review and meta-analysis of RCTs. Medline and Embase without language restriction from inception to June 15, 2024, were searched. Included RCTs had to compare mixed LA to long-acting LA in adult surgical patients for onset or duration of nerve blocks. Onset time to surgical block was the primary outcome. The Cochrane Risk of Bias Tool with GRADE methodology was utilized to assess evidence quality.

Results Nineteen trials including 1060 participants met the inclusion criteria. Mixed LA modestly reduced time to surgical block (-8.4 minutes; 95% CI -12.0 to -4.8 minutes; p = 0.0001; I² = 0.99), sensory block duration (-226.2 minutes; 95% CI -352.2 to -100.1 minutes; p = 0.002; I² = 0.98) and motor block duration (-259.2 minutes; 95% CI -399.5 to -119.0 minutes; p = 0.003; I² = 0.98) but not time to analgesic request duration (-130.5 minutes; 95% CI -265.9 to 4.9 minutes; p = 0.057; I² = 0.98). GRADE scoring ranged from low to very low.

Conclusion The existing evidence showed mixed LA led to a modest reduction in surgical block latency but also shortened block duration. Future studies should evaluate the role of mixed LA in lower limb blocks and optimal dosing of long-acting LA to balance onset latency and analgesic duration.

PROSPERO registration CRD42024552801.

Keywords
Conduction anesthesia; Local anesthetic; Nerve block

Outcomes	Definitions
Surgical block	Surgery ready block, including a composite of motor and sensory deficit, complete sensory or motor block
Surgical block latency	Time to achieve surgical block
Composite block	A composite of both motor and sensory block
Composite block latency	Time to achieve composite block
Early sensory block	Earliest presence of any sensory deficit
Early sensory block latency	Time to achieve early sensory block
Complete sensory block	A sensory block beyond early sensory block. Ex. dullness or insensate to touch, pinprick or cold
Complete sensory block latency	Time to achieve complete sensory block
Early Motor block	Earliest presence of any motor deficit
Motor block onset latency	Time to achieve early motor block
Complete motor block	A motor block beyond early motor block. Ex. Profound weakness to absent motion
Complete motor block latency	Time to achieve complete motor block
Analgesic duration	Time to onset of pain, analgesic request or a prespecified pain score, as defined by each study

Demographic					Block Detail		Local Anesthetics
Trial	Year	Total (n)	Outcome analyzed	Surgery	Type of Block	Technique	Long-Acting Local Anestheticsa	Mixture of Local Anestheticsa	Adjuvantsb	Risk of Bias
Abdelhady et al.	2022	66	Insensate to pinprick	Brachiocephalic fistula	Axillary	U/S	Bupivacaine 0.5% 30 mL	Bupivacaine 0.5% 15 mL		High
Abdelhady et al.	2022	66	Insensate to pinprick	Brachiocephalic fistula	Axillary	U/S	Bupivacaine 0.5% 30 mL	Lidocaine 2% 15 mL		High
Almasi et al.	2020	87	Insensate to touch	Hand and forearm	Axillary	U/S	Bupivacaine 0.5% 20 mL	1. Bupivacaine 0.5% 15 mL		Low
							Bupivacaine 0.5% 20 mL	Lidocaine 2% 15 mL
							Saline 10 mL	2. Bupivacaine 0.5% 20 mL
							Saline 10 mL	Lidocaine 2% 10 mL
Aguilera et al.	2024	40	≥ 14/16 scale of motor-sensory block	Forearm, wrist and hand	Infraclavicular	U/S	Bupivacaine 0.5% 35 mLc	Bupivacaine 0.5% 17.5 mL	Epinephrine 1:200,000	Low
Aguilera et al.	2024	40	≥ 14/16 scale of motor-sensory block	Forearm, wrist and hand	Infraclavicular	U/S	Bupivacaine 0.5% 35 mLc	Lidocaine 2% 17.5 mLc	Epinephrine 1:200,000	Low
Bobik et al.	2020	63	Dullness to pinprick	Forearm and hand	Axillary	U/S + Stim	1. Bupivacaine 0.375% 30 mLc	Bupivacaine 0.5% 15 mL	Epinephrine 1:200,000	Low
Bobik et al.	2020	63	Dullness to pinprick	Forearm and hand	Axillary	U/S + Stim	2. Ropivacaine 0.5% 30 mL	Lidocaine 2% 15 mLc	Epinephrine 1:200,000	Low
Bouaziz et al.	1998	34	Duration of blockg	Hand	Midhumeral	Stim	Bupivacaine 0.5% 20 mL	Bupivacaine 0.5% 10 mL		High
Bouaziz et al.	1998	34	Duration of blockg	Hand	Midhumeral	Stim	Bupivacaine 0.5% 20 mL	Lidocaine 2% 10 mL		High
Chen et al.	2013	60	Insensate to pinprick	Knee	Sciatic	Stim	Ropivacaine 0.75% 10 mL	Ropivacaine 0.75% 10 mL		Some concerns
Chen et al.	2013	60	Insensate to pinprick	Knee	Sciatic	Stim	Saline 10 mL	Lidocaine 2% 10 mL		Some concerns
Cuvillon et al.	2009	82	Surgery readyf	Lower limb	Femoral and Sciatic	Stim	1. Bupivacaine 0.5% 40 mLc,d	1. Bupivacaine 0.5% 20 mL	Epinephrine 1:200,000	Low
							1. Bupivacaine 0.5% 40 mLc,d	Lidocaine 2% 20 mLc,d
							2. Ropivacaine 0.5% 40 mLc,d	2. Ropivacaine 0.5% 20 mL
							2. Ropivacaine 0.5% 40 mLc,d	Lidocaine 2% 20 mLc,d
Freitag et al.	2006	96	Insensate to pinprick	Forearm, wrist and hand	Axillary	Stim	Ropivacaine 0.75% 40 mL	1. Ropivacaine 0.75% 10 mL		Low
								Prilocaine 1% 30 mL
								2. Ropivacaine 0.75% 20 mL
								Prilocaine 1% 20 mL
Gadsden et al.	2011	69	Insensate to pinprick	Shoulder arthroscopy	Interscalene	U/S + Stim	Bupivacaine 0.5% 30 mL	Bupivacaine 0.5% 15 mL		High
Gadsden et al.	2011	69	Insensate to pinprick	Shoulder arthroscopy	Interscalene	U/S + Stim	Bupivacaine 0.5% 30 mL	Mepivacaine 1.5% 15 mL		High
Kim et al.	2011	60	Complete loss of sensation	Upper extremity	Supraclavicular	U/S	Ropivacaine 1% 20 mL	Ropivacaine 1% 20 mL	Epinephrine 1:200,000	Some concerns
Kim et al.	2011	60	Complete loss of sensation	Upper extremity	Supraclavicular	U/S	Saline 10 mLc	Chloroprocaine 3% 10 mLc	Epinephrine 1:200,000	Some concerns
Laigle et al.	2012	30	Surgery readyf	Foot	Sciatic	U/S	Ropivacaine 0.75% 30 mL	Ropivacaine 0.75% 15 mL		High
Laigle et al.	2012	30	Surgery readyf	Foot	Sciatic	U/S	Ropivacaine 0.75% 30 mL	Mepivacaine 1.5% 15 mL		High
Laur et al.	2012	95	Reduced sensation to cold	Distal upper extremity	Infraclavicular	Stim	Bupivacaine 0.5% 40 mL	Bupivacaine 0.5% 20 mL	Epinephrine 1:200,000	Low
Laur et al.	2012	95	Reduced sensation to cold	Distal upper extremity	Infraclavicular	Stim	Bupivacaine 0.5% 40 mL	Mepivacaine 1.5% 20 mLc	Epinephrine 1:200,000	Low
Martin et al.	1993	60	Dullness to pinprick	Upper limb distal to shoulder	Axillary	Stim	Bupivacaine 0.25% 44 mLc	Bupivacaine 0.25% 22 mL	Epinephrine 1:400,000	Some concerns
Martin et al.	1993	60	Dullness to pinprick	Upper limb distal to shoulder	Axillary	Stim	Bupivacaine 0.25% 44 mLc	Lidocaine 1% 22 mLc	Epinephrine 1:400,000	Some concerns
Ozmen et al.	2013	120	Surgery readyf	Forearm or hand	Infraclavicular	Stim	Bupivacaine 0.5% 20 mL	Bupivacaine 0.5% 10 mL		Some concerns
Ozmen et al.	2013	120	Surgery readyf	Forearm or hand	Infraclavicular	Stim	Bupivacaine 0.5% 20 mL	Lidocaine 2% 10 mL		Some concerns
Pongraweewan et al.	2016	90	Insensate to pinprick	Arteriovenous fistula	Infraclavicular	U/S + Stim	Bupivacaine 0.5% 30 mL	Bupivacaine 0.5% 20 mL		Low
Pongraweewan et al.	2016	90	Insensate to pinprick	Arteriovenous fistula	Infraclavicular	U/S + Stim	Bupivacaine 0.5% 30 mL	Lidocaine 2% 10 mL		Low
Rohan et al.	2014	75	Complete loss of sensation	Upper extremity	Supraclavicular	Stim	Ropivacaine 0.75% 20 mL	Ropivacaine 0.75% 20 mL	Epinephrine 1:200,000	Low
Rohan et al.	2014	75	Complete loss of sensation	Upper extremity	Supraclavicular	Stim	Saline 10 mL	Lidocaine 2% 10 mLc	Epinephrine 1:200,000	Low
Sripriya et al.	2023	63	16/16 scale sensory motor block	Upper extremity	Supraclavicular	U/S	Bupivacaine 0.5% 20 mLc	Bupivacaine 0.5% 10 mL	Epinephrine 1:200,000	Low
Sripriya et al.	2023	63	16/16 scale sensory motor block	Upper extremity	Supraclavicular	U/S	Bupivacaine 0.5% 20 mLc	Lidocaine 2% 10 mLc	Epinephrine 1:200,000	Low
Valery et al.	2013	60	Complete loss of sensation	Leg	Sciatic	U/S + Sim	1. Ropivacaine 0.75% 5 mL	Ropivacaine 0.75% 5 mL		Low
Valery et al.	2013	60	Complete loss of sensation	Leg	Sciatic	U/S + Sim	2. Ropivacaine 0.75% 10 mL	Lidocaine 1% 5 mL		Low
Zupcic et al.	2017	85	Change to pinprick and temperature	Breast and axillary node	Paravertebral T2-T4	U/S + Stim	Levobupivacine 0.5% 21 mLe	Levobupivacine 0.5% 14 mL		Some concerns
Zupcic et al.	2017	85	Change to pinprick and temperature	Breast and axillary node	Paravertebral T2-T4	U/S + Stim	Levobupivacine 0.5% 21 mLe	Lidocaine 2% 7 mLe		Some concerns

Mixed local anesthetic compared to long-acting local anesthetic only for peripheral nerve block
	Anticipated absolute effects (95% CI)		N° of participants (studies)	Certainty of the evidence (GRADE)
Outcomes	Long-acting local anesthetic only	Mixed local anesthetic	N° of participants (studies)	Certainty of the evidence (GRADE)
Surgical block latency	The mean time to surgical block ranged from 6-38 min	MD 8.4 min lower (12 lower to 4.8 lower)	1026 (18 RCTs)	⨁⨁◯◯ Lowa
Complete block latency	The mean time to surgical block ranged from 6-38 min	MD 11.1 min lower (14.6 lower to 7.7 lower)	271 (5 RCTs)	⨁⨁◯◯ Lowa
Complete sensory block latency	The mean time to complete sensory block was 6-38 min	MD 7.8 min lower (12.6 lower to 3.0 lower)	561 (10 RCTs)	⨁⨁◯◯ Lowa
Complete motor block latency	The mean time to complete motor block was 7-65 min	MD 10.4 min lower (23.4 lower to 2.6 higher)	401 (7 RCTs)	⨁⨁◯◯ Lowa
Early sensory block latency	The mean onset of any sensory block was 2-23 min	MD 3.7 min lower (6.7 lower to 0.6 lower)	381 (6 RCTs)	⨁◯◯◯ Very lowa,b,
Early motor block latency	The mean onset of any motor block was 6-10 min	MD 1.3 min lower (8.4 lower to 5.7 higher)	184 (3 RCTs)	⨁◯◯◯ Very lowa,b,c
Duration of sensory block	The mean duration of sensory block was 227-1758 min	MD 226.2 min lower (352.2 lower to 100.1 lower)	657 (12 RCTs)	⨁⨁◯◯ Lowa
Duration of motor block	The mean duration of motor block was 466-1704 min	MD 259.2 min lower (399.5 lower to 119 lower)	551 (10 RCTs)	⨁⨁◯◯ Lowa
Duration of analgesia	The mean duration of analgesia was 264-2298 min	MD 130.5 min lower (265.3 lower to 4.9 higher)	591 (11 RCTs)	⨁⨁◯◯ Lowa

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Sociedade Brasileira de Anestesiologia (SBA) Rua Professor Alfredo Gomes, 36, Botafogo , CEP: 22251-080 , tel: +55 (21) 97977-0024 - Rio de Janeiro - RJ - Brazil
E-mail: editor.bjan@sbahq.org

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[TFN1] ^a
Pre-mixed local anesthetic concentration and volume.

[TFN2] ^b
Final concentration of adjuvant in the mixture.

[TFN3] ^c
Adjuvant added.

[TFN4] ^d
Twenty mL at femoral and 20 mL at sciatic nerve.

[TFN5] ^e
Seven mL per paravertebral level

[TFN6] ^f
Endpoint of measurement not clearly defined.

[TFN7] ^g
Study not included for primary outcome analysis.

U/S, Ultrasound; U/S + Stim, Ultrasound and Stimulator; Stim, Stimulator.