Post-operative analgesia is crucial for early rehabilitation in thoracic surgery, as patients are required to actively participate in respiratory physiotherapy.1,2 Uncontrolled pain requires high doses of opioid analgesics which should be avoided according to the Early Recovery After Surgery (ERAS) guidelines.3 An opioid-sparing analgetic regimen is used to alleviate their numerous side effects, such as nausea, vomiting, constipation, lethargy, and respiratory depression.4 Regional techniques have been implemented to reduce the need for opioid analgesics.5,6
In an attempt to find safe and less invasive methods of postoperative analgesia, new techniques of nerve blocks have emerged. Among other peripheral blocks, intercostal nerve block (ICNB) and
The ICNB applied intrathoracically at the end of the surgery, is a regional technique currently used for video-assisted thoracoscopic (VATS) procedures at our surgical center. While fairly simple to use and applied under direct vision, there are some disadvantages of the ICNB: limited time of analgesic effect, which cannot be extended by a continuous infusion, application at the end of surgery instead of pre-incision and multiple injections that are needed to pertain a single block. The block cannot be executed in the presence of pleural infection, e.g., empyema.12,13,14
The
We compared the continuous ultrasound-guided ESPB with ICNB to evaluate their analgetic efficacy in patients after lung cancer resection, representing our institution's first study of continuous ESPB in Slovenia. We present the following article in accordance with the CONSORT reporting checklist.
The study was approved by the National Ethics Committee under the number 0120-372/2019/7 and the study was registered to the Clinical Trial Registry under number NCT04665531.
Sixty participants were enrolled between the 19th of February 2020 and the 14th of March 2022. Eligible patients with early-stage lung cancer were scheduled for VATS tumor resection with a three-port approach. 80% had lung lobe resection, 12% had marginal lung resection, and 8% had segmentectomy. Most of the patients had lung adenocarcinoma (72%), followed by epidermoid or squamous cell carcinoma (20%), small-cell lung carcinoma (2%), and metastasis (2%). Two tumors turned out to be benign.
Other inclusion criteria were ASA status I–III and informed written consent for participation in the study. Exclusion criteria were chronic pain syndrome, chronic opioid use, weight less than 50 kg due to risk of local anesthetic systemic toxicity (LAST), body mass index (BMI) > 35, pregnancy or breastfeeding, allergy to local anesthetics, inflammation at the catheter insertion site or inability to use the patient-controlled analgesia (PCA) pump. Patients were randomly assigned to either the intervention ESPB arm or the comparative ICNB arm. The study protocol could not be blinded because of the indiscrete intervention type.
Patients in the ICNB group received a single-shot intrathoracic ICNB after tumor extraction, approximately 30 minutes before the end of the surgery. They received 20 ml of 0.5% levobupivacaine with injections at 6 intercostal spaces, adjacent to the surgical wound. The perineural intercostal space was located under direct vision. The same surgeon performed all the surgeries and executed the ICNBs.
Patients in the ESPB group received a 20 ml bolus of 0.5% levobupivacaine through the ESPB catheter approximately 30 minutes before the end of the surgery, continued by an infusion of 5 ml/h 0.2% ropivacaine with intermittent boluses of 15 ml per 4 hours.
Two anesthesiologists, experienced in regional anesthesia, were inserting catheters to the patients before the surgery in the pre-op area. The standard monitoring and i.v. canal were applied before the intervention. The ESPB catheter insertion was performed using Samsung© ultrasound with a GE 12L-RS high-frequency linear probe. Aseptic conditions were guaranteed by using sterile drapes, sterile probe dressings, gloves, masks, and surgical gowns. The catheter insertion underwent in a pronated position with the patient lightly sedated by 1–2 mcg/kg fentanyl. The insertion site was infiltrated with 2 ml of 2% lidocaine on the T4 level of the spine, approximately 3 cm ipsilateral from the midline on the transverse process. The needle was then inserted under ultrasound guidance, positioning the needle tip immediately above the periosteum. The position was confirmed by injecting approximately 10 ml of 0.9% sodium chloride solution, which caused a hydro-dissection between the
Ultrasound image of the inserted ESPB catheter (marked by an arrow) and interfascial hydro-dissection.
1 – underlying thoracic lamina, 2 – m.
All the patients underwent the same anesthesia protocol. Induction to general anesthesia was conducted with 1.5–2 mg/kg propofol 1% and 0.75–1 mcg/kg remifentanil in a slow bolus followed by 0.6 mg/kg rocuronium. Total intravenous anesthesia was maintained with an infusion of 5 mg/kg/h propofol 1% and 0.02–0.03 mcg/kg/min remifentanil. Blood pressure was maintained with fluid administration and appropriate vasoactive drugs when needed. Reversion of neuromuscular block was performed by a bolus of 2 mg/kg sugammadex at the end of the surgery.
Patients were constantly monitored (ECG, pulse oximetry, invasive blood pressure) from admission to the pre-op area until at least 48 hours after surgery. Nurses at the intensive care unit documented the post-operative numerical rating scale for pain (NRS) every hour in the first 48 hours except when the patient was asleep. The patients expressed their current NRS on a scale from 0 to 10 with 0 meaning no pain and 10 meaning the worst pain imaginable. Nurses asked the patients about their NRS at rest and at cough in the last hour, which included spontaneous and active cough but not respiratory physiotherapy.
Every patient received a PCA pump with the protocol: demanded bolus 3 mg piritramide 1 mg/ml per 15 min with a maximum of 2 boluses per hour with no continuous infusion. If the pain reported by a patient was still higher than 3/10, a nurse applied an additional bolus of 3 mg piritramide. When a patient demanded more than 4 boluses per hour, the attending doctor initiated an infusion of 2 mg/h piritramide until the pain settled below 3/10. All the patients received regular doses of diclofenac and metamizole in terms of multimodal analgesia.
The postoperative care of the ESPB catheter followed the same protocol as for the thoracic-epidural catheter. The attending physician evaluated the catheter insertion site every day, looking for signs of infection.
All the patients performed maximal inspiratory and expiratory pressure (MIP/MEP) tests three times: on the day of the surgery prior to the surgical procedure, 24 and 48 hours later.
The statistical analyses were performed using IBM SPSS version 25, Orange data mining and visualization suite.22 The patient and treatment characteristics were described using descriptive statistics. Demographic variables were compared with Pearson's Chi-square test. Cumulative piritramide use and NRS values are expressed as means with standard deviation. The potential differences between arms were assessed using the Kruskal-Wallis test. All the reported p-values are two-tailed with a significance level
Patient allocation and follow-up are shown in the Consolidated Standards of Reporting Trials (CONSORT) flow diagram (Figure 2).
CONSORT flow diagram.
ESPB
There were no statistically significant demographic differences between the study groups considering gender, age, body mass index, type of surgery, ASA and forced expiratory volume in the first second (FEV1) (Table 1).
Demographic data
Patients enrolled | 50 | 25 | 25 | |
Gender (male/female) | 30/20 | 17/8 | 13/12 | 0.25 |
Age (years)* | 69.80 ± 8.41 | 69.44 ± 8.20 | 70.2 ± 8.76 | 0.53 |
Height (cm)* | 170.20 ± 8.49 | 172.04 ± 8.01 | 168.36 ± 8.72 | 0.15 |
Weight (kg)* | 76.62 ± 14.07 | 76.24 ± 14.36 | 77.00 ± 14.03 | 0.72 |
BMI (kg/m2)* | 26.37 ± 3.93 | 25.72 ± 4.18 | 27.03 ± 3.64 | 0.21 |
ASA 1/2/3 | 1/25/24 | 0/14/11 | 1/11/13 | 0.47 |
FEV1 before the surgery | 94.78 ± 21.57 | 95.45 ± 21.84 | 94.17 ±21.77 | 0.88 |
Values under age, height, weight, and BMI are given as mean and 95% confidence interval.
ASA = American Society of Anesthesiologists assessment; BMI = body mass index; ESPB =
The cumulative piritramide use in the first 48 hours after surgery was 21.64 ± 14.22 mg in the ESPB group and 38.34 ± 29.91 mg in the ICNB group (p = 0.035) (Figure 3). Figure 4 shows the cumulative linear graph of piritramide use in time for each group.
Cumulative piritramide use in the first 48 hours after surgery. The values in the graph are marked as mean (blue), median (yellow), and interquartile range.
ESPB
Cumulative opioid consumption in the first 48 h after surgery. The bold line shows the median values for each group.
The mean NRS scores at rest in the first 48 hours after surgery were 1.19 ± 0.73 in the ESPB group and 1.77 ± 1.01 in the ICNB group. The difference between groups is statistically significant (p = 0.039). The mean NRS scores at cough in the first 48 hours after surgery were 2.53 ± 1.23 for ESPB and 2.85 ± 0.98 for ICNB. The difference between groups is statistically insignificant (p = 0.432).
There were no statistically significant differences between the ESPB and ICNB groups in MIP or MEP after 24 or 48 hours (Table 2).
Maximal inspiratory and expiratory muscle strength
MIP | 24 hours | 71.58 ± 16.69 | 75.98 ± 24.04 | 0.088 |
48 hours | 73.42 ± 19.10 | 88.11 ±30.72 | 0.110 | |
MEP | 24 hours | 73.36 ± 20.82 | 85.55 ± 37.35 | 0.182 |
48 hours | 74.90 ± 22.39 | 98.90 ± 32.29 | 0.645 |
Respiratory test values are expressed as percentages from the baseline value.
ESPB
Time to chest tube removal was 4.13 ± 2.92 days in the ESPB group
There were no catheter-related complications such as clogging of the catheter, unintentional removal, or insertion-site infections. Attending physicians noted a few cases of minimal bleeding under the see-through coverings.
In the ESPB group, they noted one case of paroxysmal atrial fibrillation, one case of paroxysmal supraventricular tachycardia, and one case of sinus tachycardia at the time of observation. In the ICNB group, they noted 6 cases of paroxysmal atrial fibrillation. These arrhythmias emerged on postoperative day 1 or 2.23 There were no other acute or sub-acute complications related to regional anesthesia.
This study of postoperative analgesia for VATS lung cancer resection, comparing continuous ultrasound-guided ESPB versus ICNB, is the first of its kind in Slovenia. Due to the Covid-19 pandemic crisis, causing limited resources and additional healthcare concerns, the time of patient recruitment was prolonged, and only 60 patients from 200 were eligible for our study in a two-year period. The most significant findings were lower opioid demands in the ESPB group (21.64 ± 14.22 mg
In recent years, some studies were comparing single-shot ICNB and ESPB with unclear advantages. In terms of postoperative opioid use, the ICNB was reported by some studies to be more efficient and by other studies to be less efficient than the ESPB.24,25 A previous pilot study demonstrated the feasibility of conducting a randomized controlled trial comparing continuous ESPB versus ICNB in patients undergoing VATS.26
Our results are consistent with Fiorelli
The mean piritramide use between the groups started to differentiate after 12 hours postoperatively, marking the time when the ICNB effect wears out. Other observed parameters, such as time to chest tube removal, hospital discharge, and complications were similar in both groups. However, continuous ESPB is more demanding from the catheter insertion procedure to regular post-operative observations.28 The main advantages of ESPB presumably come from prolonged local anesthetic administration, enabling individual adjustments according to NRS scores.29
Despite the continuous neuromuscular block of the hemi-thoracic musculature, the ability to fully perform respiratory physiotherapy was not compromised by the continuous ESPB. MIP and MEP measurements decreased substantially but did not differ significantly between the two groups after 24 hours or after 48 hours. Because the absolute MIP and MEP results vary strongly in literature, we included relative values with the patients’ pre-operative measurements as the baseline.30,31,32
As common complications after lung resection, cardiac arrhythmias were monitored.33 Clinicians detected no arrhythmias as a consequence of local anesthetic administration, showing there were no cases of local anesthetic cardiotoxicity. The observed arrhythmias emerged later and were attributed to other post-operative factors.
Comparing ESPB to a placebo without regional anesthesia would be unethical considering the benefits of regional truncal blocks that have already been proven.34 The ICNB's efficacy has been assessed in a large meta-analysis of 66 eligible studies.35 The ICNB is reported to be superior to systemic analgesia, non-inferior to thoracic-epidural anesthesia, and marginally inferior to paravertebral block in the first 24 hours after surgery. The data suggests that the analgetic benefit of the ICNB slowly vanishes in 24 to 48 hours after surgery. Therefore, it is a reasonable comparison in 48 hours after surgery.
The main limitation of the study is the inability to double-blind the analgesic method because of the catheter. The second limitation is the number of included patients. It would be reasonable to conduct another study on a larger scale to see whether any other inter-group differences appear. The third limitation is the protocol for the continuous ESPB, which is subject to future changes regarding local anesthetic selection and administered volume. Ropivacaine is currently the best local anesthetic of choice because of its large safety profile and the lowest potential risk for cardiotoxicity36, while new anesthetics such as liposomal bupivacaine are being researched.37
The study in our institution showed that the continuous ESPB decreases total opioid consumption and subjective pain perception at rest in the first 48 hours after VATS lung tumor resection compared to the intrathoracic ICNB. On the other hand, ESPB demands more nursing care. Regarding time to chest tube removal, hospital discharge, NRS values at cough and respiratory muscle strength, there were no observed differences between ICNB and ESPB.