Introduction

Peripheral nerve blocks (PNBs) are used more frequently as the primary anesthetic or combined with intravenous anesthetics as multimodal anesthesia for various orthopedic surgical procedures.¹ Local anesthetics (LA) have varying onset time and duration of effect, leading to clinical classification as short-, intermediate-, and long-acting LA based on pharmacodynamic and pharmacokinetic properties.^2–6

Table 1 Baseline & Perioperative Characteristics

During lengthy surgical procedures, a long-lasting PNB is preferable, requiring the use of a long-acting LA. A shorter block duration may be adequate in short surgeries, especially when limited postoperative pain is expected. A quick onset time may be favored in a fast-paced work setting, and a short or intermediate block duration may also enable patients to begin early postoperative mobilization. The effects of combining LA for peripheral nerve blocks are poorly understood. Still, clinicians may combine different categories of LA to affect the onset time, duration, and quality of a peripheral nerve block.^6–10

A common rationale for combining a short-acting with a long-acting local anesthetic may pertain to a faster block onset, while still maintaining prolonged anesthesia and analgesia on par with sole use of a long-acting local anesthetic. Thus, achieving a potentially ideal block with a fast onset and long duration.¹¹

Prior studies have primarily found that combining short- or intermediate-acting LAs with long-acting LA significantly reduces block onset and duration compared to long-acting LAs.^12–19 However, other studies have found no significant difference in block characteristics when combining LAs.^9,20,21

The infraclavicular brachial plexus block (IBPB) is a commonly used PNB.²² Few studies have investigated the effects of combining different categories of LA in an IBPB.^17,23,24 None of these have investigated the combination of lidocaine with ropivacaine in an IBPB, solely focusing on bupivacaine as the long-acting LA.

We aim to expand the research on how combining local anesthetics affects block duration by exploring the impact of lidocaine-epinephrine and ropivacaine on analgesia length after hand or wrist surgery with an IBPB. Furthermore, we aimed to evaluate patients’ satisfaction with the nerve block at postoperative follow-up.

Materials and Methods

Our hospital directorate approved this single-center retrospective cohort study as part of an observational quality assurance study (service evaluation) investigating peripheral nerve blocks for surgery. As such, approval from The Scientific Ethics Committees was waivered. Before scheduled surgery and data collection, informed consent and e-signatures were obtained from all included patients. Data was hereafter collected over the following 24 hours. An internal statistical analysis plan was composed before data extraction and statistical analyses. The present paper is written in accordance with “Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Guidelines for reporting observational studies”.²⁵

Setting and Population

Data was collected from 13^th September 2021 to 13^th September 2022 at the Departments of Anaesthesia and Orthopaedic Surgery at the Copenhagen University Hospital – North Zealand, Hillerød, Denmark. We included patients over 18 years of age scheduled for elective hand or wrist surgery in an outpatient setting. Indications for surgery included distal radius fractures, distal antebrachium fractures, osteoarthritis, metacarpal fractures, Dupuytren’s contracture, carpal tunnel syndrome, tendon ruptures, and ligament ruptures. All patients were scheduled for surgery with an IBPB as the sole type of anesthesia. No other adjuvants, anxiolytics, sedatives, or hypnotics were administered during the preoperative, intraoperative, or post-operative period, as this is not standard practice in our elective surgery unit. All patients were prescribed a standard regimen of 1000 mg acetaminophen (paracetamol) four times daily with or without 400 mg ibuprofen three times daily (depending on need, allergies, or intolerance). Prescribed opioids were either 10 mg morphine or 5 mg oxycodone up to 6 times daily depending on the patients’ analgesic needs.

Data Sources and Validation

The patient and treating anesthesiologist registered baseline data at the bedside in the Research Electronic Data Capture (REDCap) application. Follow-up data regarding “Total block duration”, “Time until block starts to subside”, “Pain after block cessation”, and “Patient satisfaction with nerve block” was registered by the patients using an SMS-based survey and registered in REDCap. Patients were instructed regarding the interpretation of survey questions and how to answer the survey via the SMS link. The survey was sent 24 hours after block administration. Unique civil registration numbers (CPR numbers) enabled data linkage and retrospective data collection from participants’ electronic health records. Authors MTS, JLT, and LHL independently validated the extracted data using predefined screening filters. If data entries did not fulfill the quality criteria, the entries were cross-checked with the patient’s electronic health records to ascertain valid entries. In the presence of inconsistencies, data entries from the electronic health record were used.

The following data were retrieved for the assessment: characteristics of the PNB (type, concentration, and volume of LA); characteristics of the patients (age, sex, body mass index (BMI), chronic opioid consumption prior to surgery); characteristics of the surgery (osseous surgery, postoperative opioid prescribed to the patient).

Intervention and Outcomes

The following LAs were used for the PNBs: lidocaine 20 mg/mL + Epinephrine 5 μg/mL (Lidokain-Adrenalin 20 mg/5 mikrog/mL, SAD, Amgros I/S, Copenhagen, Denmark) and ropivacaine 5 mg/mL (Ropivacaine 5 mg/mL, Fresenius Kabi AB, Uppsala, Sweden).^2–6 The type and volume of LA used for the IBPB and the applied method of combining LA were decided by the attending anesthesiologist performing the block. For outcome assessment, the combination of lidocaine-epinephrine and ropivacaine served as the comparator (COMBI group), while pure ropivacaine served as the control (ROPI group).

Primary Outcome

• “Total block duration” was defined as the time from a successful block, as assessed by the providing anesthesiologist, to return to baseline sensory function reported by the patient.

Secondary Outcomes

• “Time until block begins to subside” was defined as the time from a successful block to the first sensation of block remission reported by the patient.
• “Pain after complete block cessation” was patient reported on a numerical rating scale (NRS) from 0 to 10 (0 defined as no sensation of pain and 10 as the worst pain imaginable) after total block cessation.
• “Patient satisfaction with nerve block” was patient-reported on a 3-point Likert Scale: Unsatisfied, Neutral, Satisfied 24 hours postoperatively.

Peripheral Nerve Block Technique

All IBPBs were performed by highly experienced attending anesthesiologists, who combined lidocaine-epinephrine and ropivacaine according to preference.

Intravenous access was established in the contralateral arm of the patients and all patients were monitored according to hospital standards (non-invasive blood pressure, pulse oximetry, and 3-lead electrocardiography).

A lateral and sagittal in-plane technique described by Klaastad et al was utilized with a high-frequency linear ultrasound probe (Sonosite Nanomaxx Ultrasound System with a 10–5 Mhz probe - Sonosite Inc., Bothell, WA, USA).²⁶ Patients were placed in a supine position. Ultrasound was used to identify the axillary artery and vein and the lateral, medial, and posterior cords of the brachial plexus when possible. The needle was inserted medial to the coracoid process and inferior to the clavicle with subsequent ultrasound-guided slow advancement and repositioning as deemed necessary. The attending anesthesiologist determined whether to use a single- or multi-shot injection technique.

Statistical Methods

Continuous variables were reported using mean ± standard deviation. Non-normally distributed variables were reported with median and interquartile ranges (IQR). Categorical variables were reported using frequencies and percentages. Where applicable, unpaired two-sample t-test (continuous variables) and Fisher’s exact test/Pearson’s Chi-square test (categorical variables) were used as a significance test. The Wilcoxon rank sum test was used if the normality assumption was not fulfilled. The Welch two-sample test was used if the assumption of equal variances was not fulfilled. Distribution was explored and investigated regarding linearity, residuals, and variance homogeneity.

We performed multivariable linear regression analyses as sensitivity analyses to adjust for predefined potential confounding factors in continuous outcomes. Data on “Total block duration”, “Time until block begins to subside”, and “Pain after complete block cessation” in the two groups were analyzed to adjust for the following potential confounders: age; sex; BMI; type, dose and volume of LA; type of surgery; chronic opioid use; and postoperative opioid prescription. “Patient satisfaction with nerve block” was analyzed dichotomously as “Satisfied” versus “Unsatisfied or Neutral”, and multivariable logistic regression analysis adjusting for confounders was performed as a sensitivity analysis.

Two-sided P-values less than 0.05 are considered statistically significant. All statistical analyses were conducted using the statistics program R version 4.3.3.

Results

166 patients who received an IBPB were screened for the study. Of these, 28 patients did not respond to the survey. Further, 35 patients were excluded from our analyses during data validation (Figure 1). In total, 103 patients (37 in the ROPI group and 66 in the COMBI group) were included in our final analyses.

Figure 1 Flowchart of study selection and data validation.

Table 1 presents the patients’ baseline and perioperative characteristics. There were baseline differences regarding sex, total volume of local anesthetic, postoperative opioids prescribed to patients, and osseous surgery.

All comparisons of outcomes are presented in Tables 2 and 3. The primary outcome, “Total block duration”, was 655±215 minutes in the COMBI group and 961±195 in the ROPI group; the mean difference was 306 minutes (95% CI 223–389), P<0.001. “Time until block begins to subside” was 396±120 minutes in the COMBI group and 642±214 minutes in the ROPI group; the mean difference was 246 minutes (95% CI 180–312), P<0.001.

Table 2 Primary Outcome

Table 3 Secondary Outcomes

Median “Pain after complete block cessation” was NRS 5.0 (IQR: 3.0–8.0) in the COMBI group and 6 (IQR: 4.0–7.0) in the ROPI group, P=0.80.

“Patient satisfaction with nerve block” was 60% (40 of 66 patients) in the COMBI group versus 38% (14 of 37 patients) in the ROPI group, P=0.042.

In alignment with unadjusted analyses, the multivariable linear regression analyses showed a significant decrease in “Total block duration” (Table 4) and “Time until block begins to subside” (Supplementary Material: Table S1) in the COMBI group when adjusting for potential confounders. Similarly, “Pain After Complete Block Cessation” was no different in the adjusted analysis (Supplementary Material: Table S2).

Table 4 Total Block Duration – Linear Regression Analyses

When adjusting for confounders, “Patient satisfaction with nerve block” was no longer significantly different (P=0.090) (Supplementary Material: Table S3).

Discussion

Our results demonstrated that a combination of lidocaine-epinephrine and ropivacaine in an IBPB for hand and wrist surgery reduced the total block duration by approximately 5 hours compared to a block with ropivacaine alone. However, the combination did not have an apparent effect on pain after complete block cessation.

The decrease in block duration aligns with earlier findings. However, these studies were not examining lidocaine-epinephrine and ropivacaine or an IBPB.^12–19

Studies on combining local anesthetics for IBPB reveal conflicting findings. Özmen et al observed faster onset and longer analgesia with lidocaine and bupivacaine, while Pongraweewan found no differences in onset or duration.^23,24 Laur reported quicker onset but unchanged duration with mepivacaine-epinephrine added to bupivacaine.¹⁷ Aguilera et al found 0.5% bupivacaine, with epinephrine and dexamethasone, prolonged analgesia and sensorimotor block compared to 0.25% bupivacaine with 1% lidocaine but had a slower onset.²⁷ Valery found no impact on analgesia with a lidocaine-ropivacaine combination in a sciatic nerve block.²¹ These differences may have arisen from variations in techniques, anesthetics, adjuvants, and study methods.

The observed significant reduction in block duration in this study has important clinical implications. Shortened block duration may benefit surgical cases where rapid postoperative mobilization or limited postoperative pain is desirable. However, achieving optimal block duration requires careful consideration of surgical context, postoperative pain management, and patient needs.

In both groups, the median pain scores were moderately high. When performing a PNB for surgery, an aim may be to achieve a long block duration. Assuming it is beneficial to be pain-free for as long as possible while the post-surgical pain intensity subsides as time passes. Despite a difference of more than five hours in block duration between the ROPI and the COMBI group, there was no apparent effect on median pain scores immediately after block cessation.

Postoperative pain after block cessation may be mitigated by adjuvants, patient counseling, peripheral nerve catheters, and multimodal oral/IV analgesics.²⁸ However, only data on postoperative opioids prescribed to the patient was available in our database. Despite a standardized regimen of prescribed postoperative analgesics, no data on patient compliance were accessible.

Patient satisfaction was higher with lidocaine and ropivacaine; however, it was statistically non-significant after adjusting for confounders. A longer-lasting nerve block may not necessarily result in higher patient satisfaction. Loss of motor function in the post-surgical period or other unaccounted factors, such as block technique and block quality during surgery, may weigh heavily on satisfaction.

The use of epinephrine as an adjuvant to lidocaine may have affected the block durations in our sample. However, it seems unlikely to have affected the observed difference in duration compared to ropivacaine alone; if anything, the difference would likely have been greater if epinephrine was not used as an adjuvant.

This study’s limitations include its retrospective, observational design and reliance on patient-reported outcomes. While efforts were made to minimize observer bias and adjust for confounding, the non-randomized nature of the data introduces potential selection bias. Additionally, recall and response bias may arise due to the difficulty of precise reporting of block cessation times, which may have been challenging for patients, potentially affecting the accuracy of duration assessments. A larger sample size and randomized controlled trials with low risk of bias are needed to validate these findings.

Since onset times were not registered, we cannot conclude whether combining lidocaine-epinephrine and ropivacaine resulted in a faster onset.

However, if the rationale for combining short- and long-acting local anesthetics is to achieve a faster onset and prolonged block duration, clinicians should carefully evaluate the potential for a significant reduction in block duration when using a lidocaine-epinephrine and ropivacaine combination.^12,18

This may be advantageous in cases of short-duration surgery and limited postoperative pain, as quick block cessation can facilitate early mobilization and reduce the risk of joint stiffness and swelling in wrist surgery.²⁹ Nonetheless, the decision to use this approach should depend, among other factors, on the type of surgery, surgical duration and the need for rapid postoperative rehabilitation and physical therapy.

Conclusion

Combining lidocaine-epinephrine and ropivacaine reduced the duration of analgesia after an infraclavicular brachial plexus block by approximately five hours. Pain after block cessation was moderately high in both groups. Patient satisfaction may be higher when performing a nerve block with combined lidocaine-epinephrine and ropivacaine versus pure ropivacaine. Confirmative results from randomized controlled trials with a low risk of bias are warranted.