Abstract

Background

Programmed intermittent bolus (PIB) is a novel method of intermittent drug delivery commonly employed in labor epidural analgesia. This study aimed to evaluate the potential benefits of PIB over continuous infusion (CI) for postoperative analgesia following upper limb surgeries distal to the mid-humerus level using ultrasound-guided infraclavicular brachial plexus block (USG-IBPB).

Methods

The USG-IBPB was performed on a total of 30 patients scheduled for upper limb surgery distal to the mid-humerus level. The patient-controlled regional analgesia pump delivered a combination of 6 mL of 0.2% ropivacaine and 2 μg/mL fentanyl via a perineural catheter as PIB in group I and as a CI in group II. The primary outcome measure was overall drug consumption, and secondary outcomes included pain scores, patient satisfaction, sensory and motor blockade, and adverse effects.

Results

The PIB group exhibited significantly lower overall drug consumption (306.20 ± 13.07 mL vs. 323.73 ± 11.79 mL; P = 0.001), a reduced need for patient-controlled analgesia boluses (3.87 ± 2.67 vs. 7.13 ± 2.36; P = 0.001), and higher patient satisfaction (91.93 ± 10.09 vs. 78.67 ± 17.57; P = 0.017) compared to the CI group. Pain scores at rest were significantly lower at the 24-hour mark (P = 0.007), and on movement, lower scores were observed after 1, 24, and 36 hours (P = 0.031, P = 0.031, and P = 0.011, respectively). Sensory block, motor block, and adverse effects were similar between the two groups.

Conclusion

PIB demonstrated superior efficacy in postoperative analgesia compared to the CI technique for upper limb surgeries distal to the mid-humerus level. Therefore, PIB may be considered an effective alternative to CI for optimal postoperative pain management.

Keywords

analgesics, brachial plexus block, fentanyl, general anesthesia, interventional, patient satisfaction, postoperative pain, ultrasonography, upper extremity

---

Introduction

The brachial plexus block has emerged as a reliable regional anesthesia technique for upper limb surgeries and is frequently used as an alternative or adjunct to general anesthesia (GA). The infraclavicular brachial plexus block (IBPB) is performed at the level of the brachial plexus cords around the axillary artery and provides anesthesia to the upper limb below the mid-humerus level. IBPB offers several advantages over the supraclavicular block, particularly avoiding complications such as pneumothorax. Furthermore, it is more effective in anesthetizing the ulnar and musculocutaneous nerves.¹ However, IBPB can be challenging due to its deeper position and angle of approach.² In order to enhance safety and harness the expanding accessibility of ultrasound technology, ultrasound guidance has become the preferred approach for conducting IBPB. Continuous infusion (CI) of drugs through perineural catheters is commonly employed to maintain analgesia for an extended period, and IBPB is well-suited for the placement of perineural catheters.³

Recently, the programmed intermittent bolus (PIB) method has emerged as a novel approach to drug delivery, allowing for intermittent administration of a larger amount of the local anesthetic solution at set intervals. PIB has been proven to be effective in labor epidural analgesia and the promising results of programmed intermittent epidural boluses suggest its potential application in peripheral nerve blocks.^4-7

The objective of this study was to assess the potential benefits of PIB compared to CI for postoperative analgesia following upper limb surgery distal to the mid-humerus level, using the ultrasound-guided infraclavicular block.

Methods

This prospective, randomized controlled study was conducted at the Department of Anesthesia and Intensive Care in collaboration with the Orthopedics Department at Government Medical College and Hospital, Chandigarh. The study obtained approval from the Institutional Ethics Committee (GMC/IEC/2019/160, 17 December 2019), registered with the Clinical Trial Registry of India (CTRI/2020/03/023131, 5 February 2020), and obtained informed written consent from 30 patients in compliance with the Declaration of Helsinki (2013).

The study included patients classified as American Society of Anesthesiologists (ASA) physical status I or II, aged between 18 and 65 years, with a body mass index (BMI) of 18 to 30 kg/m², regardless of gender. The patients scheduled for upper limb surgery distal to the mid-humerus level, such as fractures of the radius or ulna, fractures of both bones of the forearm, the distal end of the humerus, or supracondylar fracture, among others, were eligible for inclusion. Patients who refused the procedure despite informed consent, had relevant drug reactions, psychiatric problems, history of drug abuse, underlying uncontrolled or serious cardiac, respiratory, metabolic, or neurological illnesses, bleeding diathesis, infection at the planned injection site, were on steroids, or were pregnant or lactating females were excluded from the study.

The primary outcome measure of this study was to compare the total 48-hour consumption of a local anesthetic-opioid drug mixture (0.2% ropivacaine and 2 micrograms per mL fentanyl) administered through the patient controlled regional analgesia (PCRA) pump. Secondary outcomes included pain assessment using the numerical rating scale (NRS) at various time intervals over the 48-hour study period (1, 4, 12, 24, 36, and 48 hours), evaluation of sensory and motor blockade, patient satisfaction, and monitoring of adverse effects, if any.

During the pre-anesthetic evaluation, morphometric data (height, weight) and demographic-clinical information (age, gender, co-morbidities) were recorded. The patients were blinded to their group allocation. The patients were briefed about the block procedure, the use of the PCRA, the NRS for pain assessment, pinprick pain evaluation, manual muscle test, and nausea grading in their local language. An ultrasound-guided block was performed before the procedure. Nasal prongs were placed to provide oxygen supplementation, and monitoring of heart rate, electrocardiogram, oxygen saturation, and non-invasive arterial blood pressure was conducted using a multichannel monitor. Peripheral intravenous access was established, and a normal saline infusion was administered. The patient was positioned propped up with the head turned to the opposite side during the block procedure. Local infiltration of the overlying skin was performed using 2% lidocaine. A linear ultrasound probe was positioned between the clavicle and the coracoid process to locate and identify the axillary artery and the hyperechoic cords of the brachial plexus as shown in Figure 1. Under continuous ultrasound guidance, a needle was inserted in-plane from the cephalad end of the probe and directed to the posterior aspect of the axillary artery. A bolus of 0.5% ropivacaine plus fentanyl was administered under ultrasound guidance. A catheter was then introduced and secured carefully on the chest. After the administration of the local anesthetic mixture, the progress of the nerve blockade was monitored at 2-minute intervals for 20 minutes. Sensory and motor block assessments were conducted, and the time taken to achieve adequate sensory and motor block was recorded.

Following induction, hemodynamic variables were monitored at regular intervals. All patients received a standardized technique of GA induction and maintenance. Intraoperatively, fentanyl was administered for analgesia, and PCA pumps were attached to the infraclavicular perineural catheter after surgery in the post-anesthetic care unit (PACU). The patients were randomly assigned to either group I or group II using coded sealed opaque envelopes based on a computer-generated numerical table. Group I received PIB of the local anesthetic-opioid mixture every 60 minutes, along with a PCRA bolus with a 30-minute lockout interval postoperatively. Group II received a CI of the local anesthetic-opioid mixture, along with a PCRA bolus with a 30-minute lockout interval postoperatively.

Postoperatively, all enrolled participants were observed in the PACU, and pain scores were assessed using the visual analog scale (VAS). Nausea and vomiting were evaluated using a categorical scoring system, and patients experiencing these symptoms were provided with antiemetic medication (metoclopramide injection).

The primary outcome of this study was the total 48 hours consumption of local anesthetic- opioid mixture (in mL). Using this data from Chen et al.’s study⁸ on total 48 hours ropivacaine PCA consumption in the PIB and CI group, estimates for mean and standard deviations were generated from the median and inter-quartile range data using the formulas mentioned in Wan et al.⁹ In order to minimize both type I and type II errors, alpha was set to 1% and power to 90%. With these parameters and a 1:1 allocation ratio, a minimum of 12 participants were required in each group. A minimum of 24 patients were to be enrolled in this study. Adjusting for 30% sample and data loss after inclusion in the study (e.g., due to catheter failure, incomplete data, patient refusal to continue with the study), 20 participants were planned to be recruited in each group.

Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS Inc., Chicago, IL, version 17.0 for Windows). The total 48-hour consumption of the local anesthetic-opioid mixture was compared using Student’s t-test. Kolmogorov-Smirnov test, Mann-Whitney U test, chi-square test, and Wilcoxon test were used for comparing continuous variables, binary variables, and ordered categorical variables, respectively. A two-way repeated-measures analysis of variance with post-hoc Scheffe’s test was employed for analyzing repeated-measures data over time. The significance level was set at 0.05.

Results

The CONSORT diagram illustrating patient enrollment is presented in Figure 2. The enrolled patients in the study exhibited similar demographic and morphometric characteristics, as shown in Tables 1 and 2. There were no significant differences between the two groups, except for body weight, which was higher in the CI group. However, BMI was similar between the groups. Preoperative investigations and vital parameters were comparable. The majority of the patients were male, had ASA grade I status, and a higher proportion had Mallampati grade 1.

The overall consumption of the local anesthetic-opioid mixture (in mL) was higher in the CI group (323.73 ± 11.79) compared to the PIB group (306.20 ± 13.07) (P = 0.001). Additionally, the median number of PCA boluses taken by patients in the PIB group was 3, whereas, in the CI group, it was 8 (P = 0.003). Patient satisfaction at the end of the study was significantly higher in the PIB group (91.93 ± 10.09) than in the CI group (78.67 ± 17.57) on a 100-point VAS (P = 0.017). Regarding pain relief, the NRS score for pain at rest was lower in the PIB group only at the 24th hour after surgery (P = 0.007) (Table 3). Pain on movement, evaluated by the NRS scale at 1, 24, and 36 hours, was lower in the PIB group compared to the CI group (P = 0.031, 0.031, and 0.011, respectively) (Table 4). There were more reported adverse effects, such as nausea, dizziness, and vertigo, in the PIB group until the 6th hour, 4th hour, and 15th minute of the study, respectively, but the differences were not statistically significant (P > 0.05 for all). No other adverse effects, such as hypotension, bradycardia, or decreased respiratory rate, were observed.

Furthermore, the study found that the time at which patients took their first PCA bolus was similar between the two groups (4.04 ± 5.37 for group I and 3.97 ± 3.55 for group II). However, the trend of bolus consumption demonstrated that patients in the CI group required more boluses starting from the 12th hour and continued to take more boluses at the 24th, 36th, and 48th hours. The median bolus consumption in the PIB group was 1, 1, 0, and 0, respectively, whereas, in the CI group, it was 2, 2, 2, and 1, respectively (P = 0.032, 0.004, 0.009, and 0.030, respectively). The perioperative vital signs were similar, except for a statistically significant difference in mean systolic blood pressure (in mmHg) between the two groups at 5 minutes (110.87 ± 10.21 for group I and 120.47 ± 14.19 for group II) (P = 0.042).

Discussion

We adhered to the recommendations of Chong et al.¹⁰ and Jagannathan et al.¹¹ regarding the outcomes of our study, which included drug consumption, patient satisfaction, pain relief, and adverse effects. We focused on patient-controlled analgesia (PCA) and selected the most painful surgeries for our investigation.

Our study results align with the findings of Chen et al.⁸ who conducted a randomized, double-blind, controlled study comparing PIB and CI for postoperative PCA in patients undergoing video-assisted thoracoscopic unilateral lung resection surgery with a thoracic paravertebral block. Similar to their findings, we also observed a significantly lower total number of PCA boluses and total drug consumption in the PIB group compared to the CI group after a 48-hour study period which suggests better pain control with PIB. Moreover, the median number of PCRA boluses taken by patients in the PIB group was 3 as in their study, while it was 8 in the CI group compared to 12 in their study. The CI group had higher overall drug consumption (in mL), while patient satisfaction was significantly higher in the PIB group. This was not consistently reflected in the pain scores since they were lower in the PIB group only at the 24th hour at rest and at 1, 24, and 36 hours on movement. Although more patients in the PIB group experienced adverse effects such as nausea, dizziness, and vertigo until the 6th hour, 4th hour, and 15th minute of the study, respectively, these differences were not statistically significant. No other adverse effects, such as hypotension, bradycardia, or decreased respiratory rate, were observed compared to the study by Higashi et al.¹²

We also noted that the time at which patients took their first PCA bolus was similar between the two groups. However, the trend of bolus consumption demonstrated that patients in the CI group required a higher number of boluses starting from the 12th hour and continued to take more boluses at the 24th, 36th, and 48th hours suggesting a lesser degree of pain control by CI. Perioperative vital signs were similar between the two groups, except for a statistically significant difference in mean systolic blood pressure at 5 minutes. This isolated and erratic finding could be attributed to various confounding factors, such as a lighter plane of anesthesia or the wearing off of muscle relaxants.

Although there were no directly comparable studies with identical methodology in our setting, several studies have compared the effectiveness of PIB and CI methods for postoperative pain relief such as the study by Chen et al.⁸. In another study by Oxlund et al.¹³, PIB and CI were compared for postoperative analgesia in 57 patients undergoing major shoulder surgery with an interscalene catheter. The PIB group received 16 mg of ropivacaine every 2 hours, while the CI group received a CI of 8 mg/hr ropivacaine with the same patient-controlled rescue analgesia. They found no significant differences in postoperative analgesia between the two groups. However, total drug consumption was significantly higher in the CI group compared to the PIB group. The number of PCA boluses was comparable between the groups and additional bolus demands during the lockout time were also similar. Therefore, they concluded that PIB could not be considered superior to CI after major shoulder surgery.

The strengths of our study include its prospective, randomized, patient-blinded clinical trial design. We strictly followed the inclusion and exclusion criteria. Despite not achieving the planned sample size of 40 patients, our study included 30 patients, which exceeded the minimum requirement of 24 patients. We included every enrolled patient in the analysis, and there were no dropouts or losses to follow up, ensuring sufficient statistical power to detect true differences. As a result, significant differences emerged in both primary and many secondary outcomes, providing robust findings. However, there were some limitations to our study. Firstly, the patients included were only classified as ASA grade I or II, so the results may not apply to patients with other ASA grades. Secondly, double-blinding was unattainable in our study design due to the need for postoperative machine adjustments, troubleshooting, and drug administration by the data collector. Thirdly, we did not assess the quality of the sensory block and motor block postoperatively, but we recorded the duration required to achieve an adequate block. Sensory block assessment using repeated neurological examination was challenging after surgery due to the application of a cast over the entire limb in our area of interest. The time at which patients took their first PCA bolus was recorded as an endpoint of the sensory block. Additionally, assessing motor blockade was impractical immediately after surgery since the repaired areas (e.g., the distal end of the radius and the distal end of the humerus) were near joints and could not be moved.

In future studies, it would be beneficial to include a larger sample size to further validate these findings.

In conclusion, our study demonstrated that patients who received a local anesthetic-opioid combination using the PIB method had lower drug consumption. The PIB method provided better pain control, as indicated by lower postoperative NRS scores, a reduced number of PCRA boluses throughout the study period, and higher patient satisfaction with insignificant adverse effects. Therefore, PIB may be considered an effective alternative to CI for optimal postoperative pain management in upper limb surgeries.

---

References