The Scalp Nerve Block Combined with Intercostal Nerve Block Improves Recovery After Deep Brain Stimulation in Patients with Parkinson’s Disease: A Prospective, Randomized Controlled Trial

Introduction

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor symptoms, such as tremors, rigidity, and bradykinesia.^1,2 More than 6.1 million people globally experience multisystem symptoms of PD.³ Deep brain stimulation (DBS) has emerged as an effective treatment modality for managing advanced PD, providing significant symptomatic relief, and improving the quality of life of patients.^4–6 Despite improvements in surgery and anesthesia, pain affects postoperative recovery in patients undergoing such surgeries due to altered pain processing and sensitization to opioids.⁷ Therefore, appropriate analgesia strategies should be adopted to PD patients scheduled for DBS surgery, which may improve the postoperative quality of recovery (QoR), shorten hospital stays, and decrease potential complications after surgery.^8,9

Multiple clinical studies have adopted peripheral nerve blocks instead of opioids to treat acute pain after surgery.^10,11 Previous studies have shown that a scalp nerve block (SNB) with ropivacaine can provide perioperative analgesia and reduce pain-related complications after craniotomy.^12,13 In addition, the intercostal nerve block (ICNB) has been reported to alleviate acute pain and reduce opioid consumption after thoracotomy.¹⁴ Therefore, SNB combined with ICNB may reduce pain and pain-related adverse events after DBS surgery because the incision sites are innervated by the scalp and intercostal nerves.

Postoperative pain and pain-related complications are important components of the 15-item QoR (QoR-15) score after surgery, which is a validated questionnaire used to assess multidimensional postoperative recovery.¹⁵ Previous studies have shown that peripheral nerve blocks improve QoR after craniotomy.¹⁶ However, few studies have explored the efficacy of SNB combined with ICNB in improving QoR after DBS surgery.

We conducted this prospective randomized controlled trial to examine the hypothesis that SNB combined with ICNB would enhance the quality of recovery after DBS surgery in patients with PD, aimed to provide suitable analgesic strategies to patients undergoing DBS surgery, and to propose a new insight for the improvement of recovery.

Materials and Methods

This single-center, prospective, double-blinded, randomized trial was performed at Changhai Hospital, Naval Medical University, Shanghai, China, from April 2022 to March 2023. Protocol¹⁷ was approved by the ethics committee of Shanghai Changhai Hospital (CHEC2022-042) on March 22, 2022, and was registered at clinicaltrials.gov (NCT05353764) on April 19, 2022. All enrolled patients provided written informed consent before surgery.

Participants

We enrolled patients with PD aged ≥18 years who underwent elective subthalamic nucleus DBS surgery, had an American Society of Anesthesiologists (ASA) physical status of I–III, and were able to communicate normally. We excluded patients who had (1) an allergy to local anesthetics, (2) pre-existing infection at the block site, (3) severe coagulopathy, (4) preoperative neuropathic pain, and (5) a history of DBS surgery.

Randomization and Blinding

Patients were randomly assigned to the SNB and control groups at a ratio of 1:1 using computer-generated random number tables by an anesthesia nurse who was not involved in the study. The anesthesia nurse typed the group assignment on separate papers, folded them up, and placed them inside sequentially numbered sealed opaque envelopes. On the day of surgery, the anesthesia nurse opened the envelopes and prepared the study drug. Anesthesia induction and blockade were performed by the same attending anesthesiologist on our study team. The attending anesthesiologist performing the blockade and the anesthesia nurse were aware of the allocation. The patients were blinded to the group allocation because the blockade was performed when they were unconscious. In addition, group assignment was concealed from another anesthesiologist responsible for operation, investigators involved in the follow-up and collecting data, surgeons, and personnel in the post-anesthesia care unit (PACU).

Anesthetic and Analgesic Managements

Anesthesia induction and maintenance were conducted in accordance with a previous protocol¹⁷ after providing standard care to the patients in the two groups. Briefly, anesthesia was induced with 8 mg of dexamethasone, sufentanil 0.3–0.5 μg kg⁻¹, propofol 2–3 mg kg⁻¹, and rocuronium 0.6 mg kg⁻¹. Anesthesia was maintained through continuous infusion of remifentanil (0.1–0.2 μg kg⁻¹ min⁻¹), and propofol (6–8 mg kg⁻¹ h⁻¹) was administered to maintain stable hemodynamics. Additionally, 10 μg of sufentanil was administered 30 min before the end of surgery, and propofol and remifentanil infusions were discontinued after surgery. After surgery, patients were transferred to the PACU without receiving patient-controlled analgesia. When the Aldrete score was ≥ 9, patients were transferred to the ward. Parecoxib sodium 40 mg was administered as rescue treatment for patients whose numeric rating scale (NRS) scores were higher than 4 in the PACU or ward. If patients experienced nausea or vomiting, they were administered 4 mg of ondansetron.

Interventions

Participants randomized to the SNB group underwent SNB and ICNB with 0.5% ropivacaine, which was performed exclusively by attending anesthesiologists after the induction of general anesthesia. A 25- gauge needle with a 10-mL syringe was used to perform landmark-guided SNB.¹⁸ After negative aspiration, the scalp nerves, including the greater occipital, auriculotemporal, supratrochlear, and supraorbital nerves, were blocked by injecting 2–3 mL of 0.5% ropivacaine bilaterally around each of the 4 nerves. The total volume of the SNB did not exceed 10 mL.

Ultrasound-guided ICNB on the surgical side was performed at the plane of T4-T5 proximal to the anterior axillary line in the supine position after SNB. After determining the optimal image, including the pleura, internal intercostal muscles, rib, and innermost intercostal muscles, an echogenic needle was inserted to target the inferior margin of the rib, using the in-plane technique. After volume aspiration, 10–15 mL of 0.5% ropivacaine was injected into the intercostal spaces. ICNB was considered successful when downward displacement of the pleura was observed in the intercostal spaces.

The block efficacy for dermatomal sensory testing was not formally tested because the patients under general anesthesia were unconscious. After the nerve blockade, the attending anesthesiologists covered the dressing in the relevant areas to hide the allocation. The participants in the control group received the same care as those in the SNB group. However, only the dressing was covered for these participants at the same site in the SNB group, without SNB or ICNB. Patients in both the SNB and control groups did not undergo local infiltration of the anesthetic and did not receive scheduled nonsteroidal anti-inflammatory drugs after surgery.

Outcome Measures

The primary outcome was the QoR-15 score 24 h after surgery. The secondary outcomes included QoR-15 scores at 72 h and 1 month after surgery; NRS pain scores (overall pain at rest) before discharge from the PACU, and at 24 h, 72 h, and 1 month after surgery; intraoperative opioid consumption; rescue analgesic use 24 h after surgery; nausea and vomiting 24 h after surgery; emergence agitation; time to respiratory recovery; time to response; time to extubation;¹⁷ duration of anesthesia and surgery; PACU length of stay; and nerve block-related adverse events.

The quality of recovery following surgery was assessed using the QoR-15 score, which includes five dimensions of recovery: pain, physical comfort, physical independence, psychological state, and emotional state.¹⁵ The total score on the QoR-15 ranges from 0 (poorest QoR) to 150 (best QoR). At the 1-month assessment, the patients answered the QoR questionnaire before receiving an explanation of their condition at the outpatient clinic. The QoR-15 questionnaire was administered by qualified investigators trained in the manual.

Sample Size and Statistical Analysis

The sample size was calculated using the QoR-15 score. A QoR-15 score change of 8 points was considered clinical improvement.¹⁹ According to our preliminary study, the QoR-15 score 24 h after DBS in PD patients without nerve block was 110 (10.1). We calculated the required number of patients using PASS 11 software with an alpha error of 0.05 and power of 95% for an 8 points difference in QoR-15 score, and determined that 35 patients would need to be included in each group. Considering the dropout rate of 20%, we defined a sample size of 88 participants.

Data analyses were primarily performed in the intention-to-treat population using R software packages and Free Statistics software, version 1.7.1. For subjects with missing data due to loss to follow-up for one month after surgery, we used available assessments. The normality of continuous variables was tested using the Shapiro–Wilk normality test. Continuous variables in normally distributed data, represented as mean ± standard deviation, were compared using the Student’s t-test, while continuous variables in non-normal distribution data, reported as medians (quartiles), were compared using the Mann–Whitney U-test. Categorical variables, described as frequencies and percentages, were compared using χ2 test or Fisher’s exact test.

Repeated measures of variables at different times in QoR-15 scores were analyzed using generalized estimating equation models adjusted for baseline characteristics (including age, sex, body mass index, ASA physical status, hypertension, diabetes, and preoperative QoR-15 scores). NRS pain scores between the two groups were compared using the Mann–Whitney U-test, which was used as an exploratory test. The association between the primary outcome and intervention was adjusted for potential confounders using multivariable linear regression analysis in the post hoc analysis, including sufentanil consumption, remifentanil consumption, rescue analgesic use, nausea and vomiting, and NRS pain score at PACU discharge and 24 h after surgery. P < 0.05 was regarded as statistically significant.

Results

One hundred and forty patients were initially assessed for eligibility in this study; however, 20 did not meet the inclusion criteria, and 32 refused to participate. Therefore, 88 patients were randomly allocated to the study group. At the time of assessment 1 month after surgery, ten and six patients in the SNB and control groups, respectively, were lost to follow-up (Figure 1). The baseline characteristics of the subjects are depicted in Table 1. No significant differences were noted between the Control and SNB groups. In addition, there were no nerve block-related adverse events in this study.

Table 1 Baseline Characteristics of the Participants

Figure 1 Flowchart of study population.

Primary Outcome Data

The primary outcome, QoR-15 score 24 h after surgery, is shown in Table 2. The QoR-15 score (mean ± standard) at 24 h after surgery was significantly higher in the SNB group than that in Control group: 122.0 ± 7.6 vs 113.5 ± 11.3 (P = 0.006).

Table 2 The QoR-15 Scores Compared Between Two Groups

Secondary Outcome Data

Similar to the primary outcome, the QoR-15 score at 72 h after surgery was higher in the SNB group than in the control group (P = 0.004). However, there were no significant differences in long-term QoR between the SNB group (n = 34) and control group (n = 38) groups (P = 0.230) (Table 2).

The other secondary outcomes are presented in Table 3. Preoperative SNB combined with ICNB reduced the NRS pain scores at PACU discharge and 24 hours after surgery (all P < 0.05). However, there were no differences in NRS scores at 72 h (P = 0.603) and 1 month (P = 0.250) after surgery between the two groups. The intraoperative mean remifentanil consumption (1.5±0.2 mg vs 1.7±0.3 mg, P = 0.017), and mean sufentanil consumption (29.5±6.9 μg vs 34.1±4.9 μg, P < 0.001) in SNB group were significantly lower than those of Control group.

Table 3 Secondary Outcomes During the Study Period

The number (%) of rescue analgesics required 24 h after surgery was lower in the SNB group (18.2%) than in the control group (45.5%) (P = 0.006). The incidence of postoperative nausea and vomiting (PONV) was lower in the SNB group (36.4%) than in the control group (61.4%) (P = 0.019). However, there were no significant differences between the two groups in the duration of anesthesia, duration of surgery, and PACU length of stay. The incidence of emergence agitation, time to respiratory recovery, time to response, and time to extubation were similar between the two groups.

Post Hoc Analyses

Because secondary outcomes may affect QoR-15 scores, we performed a post hoc analysis of the association between nerve block and QoR-15 scores 24 h after surgery. After adjusting for variables with P < 0.05, as shown in Table 3, nerve block was positively related to QoR-15 scores 24 h after surgery (β = 8.92; 95% CI = 4.52~13.32) (Table 4).

Table 4 Multivariable Linear Regression Analysis to Assess the Association Between Nerve Block and QoR-15 Scores at 24 h After Surgery

Discussion

This prospective randomized controlled trial aimed to investigate the effect of preoperative SNB combined with ICNB on the quality of recovery after DBS surgery in patients with Parkinson’s disease. We found that patients who underwent preoperative SNB combined with ICNB reported higher QoR-15 scores than those in the control group at 24 and 72 h after surgery after adjusting for baseline characteristics. In addition, patients in the intervention group had reduced intraoperative opioid consumption, decreased postoperative rescue analgesic use, low incidence of PONV, and superior pain relief in the early postoperative period. No nerve block-related adverse events (eg, local anesthetic toxicity, pneumothorax, bleeding, or infection) were observed. These findings indicate that preoperative SNB combined with ICNB may be an effective intervention to enhance recovery after DBS in patients with PD.

QoR-15 is an outcome questionnaire reported by patients that assesses the quality of recovery following surgery and anesthesia.²⁰ The QoR-15 score involves many areas beyond the scope of postoperative pain, which is consistent with Standardized Endpoints in Perioperative Medicine initiatives.²¹ In addition, the QoR-15 questionnaire has the same psychometric properties, but is more feasible to use than the QoR-40.²² Therefore, we chose the QoR-15 score 24 hours after surgery as the primary outcome.

Previous studies have demonstrated that peripheral nerve blocks alleviate pain and enhance the QoR after surgery.^23–25 In this study, we found that preoperative SNB combined with ICNB enhanced the short-term QoR-15 score after DBS surgery but not 1 month after surgery. However, QoR-15 scores may be affected by intraoperative variables. After adjusting for potential confounders, the intervention was associated with higher QoR-15 scores 24 hours after surgery. Therefore, our results indicate that preoperative SNB combined with ICNB led to significantly better postoperative short-term health status of patients after DBS surgery, which is consistent with previous studies.^16,26

In addition to the improvement in the quality of recovery, our study also showed opioid-sparing properties and better analgesia with preoperative SNB combined with ICNB. We found that patients who received intervention before surgery had lower pain scores at PACU discharge and 24 hours after surgery than those in the control group. However, the statistical differences did not last longer than 24 hours, which may be attributed to the pharmacokinetic features of ropivacaine. Consistent with many studies,^27,28 preoperative SNB combined with ICNB also decreased the intraoperative opioid consumption. High opioid consumption results in numerous adverse events such as respiratory depression, nausea, vomiting, and bowel ileus.^29,30 Therefore, SNB combined with ICNB instead of opioids to prevent acute postoperative pain could be a promising component of a multimodal analgesic approach in DBS surgery.

In this study, we also showed that patients receiving SNB combined with ICNB had a lower incidence of PONV and rescue analgesic use 24 hours after surgery. Most likely, the prolonged time in which SNB combined with ICNB provided pain relief, lower pain scores, and decreased intraoperative opioid consumption may have reduced PONV and rescue analgesic use. Previous studies have also reported that peripheral nerve blocks are associated with a significantly lower risk of PONV and rescue analgesic use after surgery.^31,32 Moreover, no nerve blockade-related complications were observed in this study, which may occur due to superficial nerves and ultrasound guidance.

Several potential mechanisms may explain the observed benefits of preoperative SNB combined with ICNB in our study. SNB and ICNB interrupt the transmission of nociceptive signals from the incisions, providing analgesia and reducing central sensitization. This reduced intraoperative opioid consumption, opioid-related side effects, and rescue analgesic use. Moreover, improved analgesia may enhance postoperative sleep quality and lower anxiety and depression levels, leading to improved postoperative recovery.

This study has several limitations. First, a formal dermatomal evaluation of block efficacy was not conducted because of unconsciousness after anesthesia, which increased the risk of incomplete block. However, complete block of the superficial nerves for SNB and ultrasound guidance for ICNB are easy to obtain, which is consistent with the routine clinical practice. Second, the Chinese version of the QoR-15 questionnaire was used in the present study, which may have distorted the results because of this study due to language and cultural differences. Third, our study was conducted at a single center, which may have introduced a potential bias. Multicenter studies are needed to confirm the efficacy and safety of preoperative SNB combined with ICNB in patients with Parkinson’s disease undergoing DBS surgery.

Conclusion

In conclusion, our study provides evidence that preoperative scalp nerve block combined with intercostal nerve block improves the quality of recovery, enhances analgesia, and reduces intraoperative opioid consumption and incidence of PONV in patients with Parkinson’s disease undergoing DBS surgery.