Comparative analysis of analgesic efficacy and functional recovery in open pancreaticoduodenectomy: a randomized controlled trial of local anesthetic wound infiltration, transversus abdominis plane block, and intramuscular electrical stimulation

Introduction

Effective pain management is a prerequisite for favorable postoperative outcomes. The use of multimodal analgesia, a key component of enhanced recovery after surgery (ERAS) pathways, is vital to achieving optimal results in various surgical procedures (1). Several ERAS protocols have been suggested for open pancreaticoduodenectomy (PD), a major extensive laparotomy. However, unlike nutritional or ambulation issues that are well-established through clinical trials, an effective pain management strategy is yet to be determined (2,3). The 2019 updated guidelines highlight that the use of local wound catheters is controversial, with concerns regarding their efficacy and patient discomfort (3).

Four-quadrant transversus abdominis plane (4QTAP) block is a regional analgesia technique that targets nerves innervating to the anterolateral abdominal skin, muscle, and parietal peritoneum (4). Its efficacy has been studied in various abdominal surgeries, showing positive effects overall. However, its effectiveness varies depending on the surgical procedure and timing of administration. While 4QTAP block has been favored over local wound infiltration (LWI) in some laparoscopic surgeries and integrated into ERAS protocols (5-7), studies on cesarean sections and lower abdominal laparotomies have shown only modest benefits, with analgesic effects similar to those of LWI (8,9). Furthermore, its effectiveness in open hepatobiliary or pancreatic surgeries lacks substantial evidence, leading to uncertainty about its inclusion in the ERAS protocol.

Needle electrical twitch obtaining intramuscular stimulation (NETOIMS), initially used to relieve pain and muscle strain in musculoskeletal disorders, demonstrates effective pain relief when combined with LWI for patients undergoing open PD (10). However, in perioperative settings where multimodal pharmacologic analgesia is utilized, performing multiple post-surgery procedures sequentially can be time-consuming and expensive. Therefore, it is essential to identify a single, optimal procedural intervention in advance through comprehensive comparisons.

Therefore, this prospective, single-blinded, randomized controlled trial aimed to determine the most effective procedure among LWI, 4QTAP block, and NETOIMS as components of multimodal analgesia in patients undergoing open PD. The functional restoration and pain profiles were assessed to provide comprehensive evidence in terms of the ERAS pathways. We present this article in accordance with the CONSORT reporting checklist (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-23-650/rc) (11).

Methods

Study design

This prospective, single-blinded, randomized controlled study was approved by the Institutional Review Board of Gangnam Severance Hospital (No. 3-2020-0471). This study was performed in accordance with the tenets of the Declaration of Helsinki (as revised in 2013). Written informed consent was obtained prior to patient enrollment.

Between January 2021 and September 2022, patients aged ≥19 years with American Society of Anesthesiologists’ physical status I–III who were scheduled to undergo PD were screened for potential enrollment. Patients with a history of abdominal surgery, drug addiction, allergies to local anesthetics or opioids, chronic pain, cognitive disorders that hindered the ability to respond to the researcher and survey, pacemakers (due to risk of electrical interference), as well as patients unable to walk independently without assistance due to locomotive disorders, were excluded. Patients who were pregnant, lactating, or fragile were also excluded. A single experienced surgeon, who performed over 50 open PD annually, was included in the study.

The patients were randomly assigned to the LWI, 4QTAP, or NETOIMS group in a 1:1:1 ratio. Randomization was carried out using R statistical software (Foundation for Statistical Computing, Vienna, Austria). Preoperatively, the closed-envelope technique was employed by a nurse who wasn’t involved in either the treatment or the study. Physicians who managed the patients postoperatively were blinded to the group allocation and study protocol.

Perioperative management

Pulse oximetry, electrocardiogram, and end-tidal CO₂ monitoring were initiated. As premedication, 0.1 mg of glycopyrrolate was injected intravenously. Subsequently, 2 mg/kg of propofol and 0.2–0.5 µg/kg of remifentanil were administered to induce anesthesia. Endotracheal intubation was facilitated using 0.8 mg/kg of rocuronium. Invasive arterial blood pressure and central venous pressure were monitored at the radial artery and internal jugular vein. The patients were ventilated with 50% oxygen with a tidal volume of 8 mL/kg, a respiratory rate of 8–14 breaths/min, and a positive end-expiratory pressure of 5 mmHg, resulting in an end-tidal CO₂ of 30 to 40 mmHg. Anesthesia was maintained with 0.6–2.0 vol% of sevoflurane and 0.05–0.2 µg/kg/min of remifentanil. All patients underwent PD via laparotomy with a 20-cm-long midline incision extending from 2 cm below the umbilicus to the xiphoid process. The surgical procedure for PD was performed as described in a previous report (12). The postoperative analgesia regimen for all patients included the administration of 50 µg of fentanyl and 0.3 mg of ramosetron 20 min before endotracheal extubation. Intravenous (IV) patient-controlled analgesia (PCA), comprising 20 µg/kg of fentanyl and 0.3 mg of ramosetron (total volume, 100 mL; infusion rate, 2.0 mL/h; bolus, 0.5 mL; lockout time, 15 min), was administered at the end of the surgery. In the postoperative analgesia care unit, patients with a pain score exceeding 4 on the visual analog scale score (VAS score: 0, no pain; 10, worst imaginable pain) were administered 1 µg/kg of fentanyl. If needed, rescue analgesics given in the ward included 50 mg of tramadol, 25 mg of pethidine, or 400 mg of ibuprofen. When the patient desired further pain control or when the patient had a pain score of 5 or higher on the visual analogue scale, intramuscular tramadol, IV ibuprofen, and intramuscular pethidine were administered in order. Additionally, 1 mg of granisetron was given as an anti-emetic on postoperative days (PODs) 1 and 2.

Interventions

Patients in the LWI group were administered LWI through an On-Q pump (ON-Q pain management system, I Flow Corp., Lake Forest, CA, USA) catheter, which was inserted at the surgical incision site following the main procedures but prior to the incision closure. Including preparation, it took approximately 1–2 minutes. As part of the On-Q pump PCA regimen, 4 mL/h of 0.5% ropivacaine (1,650 mg) was administered to the patients until POD 3. The PCA was maintained until the removal of the catheter on POD 3. Two surgeons, each with experience in performing over 100 On-Q pump catheter insertions annually, were included in the study.

For the 4QTAP block group, a 4QTAP block was administered under ultrasound guidance (see Video S1) immediately after anesthesia induction and before the surgery (13). Subsequently, a solution of 10 mL of 0.375% ropivacaine with 1:200,000 epinephrine was injected into the plane between the rectus abdominis and transversus abdominis muscles on both sides (subcostal blocks) and between the internal oblique and transversus abdominis muscles on both sides (lateral blocks). Two anesthesiologists, each with experience in executing over 100 4QTAP blocks annually, participated in the study. The time required for the 4QTAP block, including preparation, was approximately 5–10 minutes.

The NETOIMS group underwent NETOIMS under ultrasound guidance immediately after surgical wound closure, as previously described (10). With a reference surface electrode affixed nearby on the skin of the target muscle, an aseptic disposable monopolar needle electrode (45 mm diameter, 50 mm length; Technomed, the Netherlands) was inserted into the target muscle’s stimulating point. Bilateral rectus abdominis muscles were targeted with seven stimulating points on each side, spaced 2 cm from the midline and aligned at dermatome levels from T5 to T11. Using a portable electrical stimulator (Clavis, Alpine Biomed ApS, Denmark), direct current stimulations with 2-ms pulse duration of unipolar negative square waves were applied to each point for 10 seconds at a 10 Hz frequency. All muscle twitches were either observed directly or visualized via ultrasonography. The study included an anesthesiologist experienced in performing over 50 NETOIMS annually. The time required for NETOIMS, including the preparation process, was approximately 5–10 minutes.

Study endpoints

The primary endpoint was the postoperative VAS pain score on POD 3. The secondary endpoints were VAS pain scores on PODs 0, 1, 2, 5, 7, 14, and 28; morphine milligram equivalents (MMEs) up to POD 3; ibuprofen consumption by POD 3; incidence of nausea and vomiting during hospital stay; peak cough flow (PCF) and gait speed on PODs 2, 7, 14, and 28. The cumulative opioid dose administered via IV PCA and as a rescue analgesic up to POD 3 was converted to MME (Figure 1).

Figure 1 Study protocol. *, primary endpoint. VAS, visual analogue scale; LWI, local wound infiltration; 4QTAP, four-quadrant transversus abdominis plane; NETOIMS, needle electrical twitch obtaining intramuscular electrical stimulation; BL, baseline; POD, postoperative day.

The pain score was assessed by a nurse who did not participate in any pain-relieving intervention. Open-ended questions were used, employing the VAS scale (0: no pain, 10: worst imaginable pain) while patients were in the supine resting position at 7 a.m. on PODs 0, 1, 2, 3, 5, 7, 14, and 28. On POD 0, which is the day of operation, the pain score was assessed immediately upon the patient’s arrival to the ward following surgery. PCF and gait speed were measured on PODs 1 (the day before the surgery, baseline), 2, 7, 14, and 28 by trained nurses, as previously described (14). To measure PCF, the patients were seated in a chair at 90° and instructed to cough into a peak flow meter (Mini-Wright Standard PFM, Clement Clarke International, England) as strongly as they could; this process was repeated thrice at each time point. The consecutive PCF measurement was obtained only after the pain elicited by the previous PCF measurement had subsided completely. Gait speed was assessed while walking straight on a level surface on a 15-m track. The patients were requested to walk as fast as possible within an acceptable pain range thrice. The patients were allowed to rest if dyspnea on exertion, dizziness, or a feeling of tiredness occurred during the measurements. The patients rested before each consecutive measurement until they felt comfortable with the surgical site. For PCF and gait speed, which were repetitively measured, the average value of each parameter was used in the final analysis.

Statistical analysis

A previous study reported that the pain score of patients who underwent PD on POD 3 was 4.05±1.57 (14). It was hypothesized that a 4QTAP block or NETOIMS would decrease the score by 40%. Thus, using an α of 0.05, power of 0.80 (two-sided test), considering a compliance rate of 80% and a possible dropout rate of 20%, 72 patients were enrolled in the study.

Continuous variables were compared using one-way analysis of variance followed by post-hoc Bonferroni analysis and are presented as mean ± standard deviation (SD). For the analysis of gait speed and PCF, the percentages of gait speed and PCF were calculated based on the values recorded on POD −1 (baseline). Categorical variables were compared using the Chi-squared test or Fisher’s exact test and are presented as the number of patients (proportion). All statistical analyses were performed using Statistical Package for the Social Sciences version 25 (IBM Corp., Armonk, NY, USA). A two-sided P value of less than 0.05, within a 95% confidence interval (CI), was deemed statistically significant.

Results

Eighty patients were screened for inclusion in the study. Eight patients were excluded due to a history of previous abdominal surgery (N=4) and refusal to participate (N=4). Two patients in LWI group and one patient each in 4QTAP block group and NETOIMS group were excluded due to changes in the surgical plan after enrollment. As a result, 68 patients were included in the final analysis (Figure 2). No complications related to LWI, 4QTAP block, or NETOIMS were reported. The demographic, preoperative and intraoperative variables were comparable, except for the dose of intraoperative remifentanil and the mean arterial pressure 1 min after skin incision, which were lower in 4QTAP block group (Table 1). Postoperative morbidity and duration of hospitalization did not differ among the groups.

Figure 2 CONSORT diagram. 4QTAP, four-quadrant transversus abdominis plane; NETOIMS, needle electrical twitch obtaining intramuscular electrical stimulation.

Postoperative pain and analgesic requirements

Pain scores, assessed via VAS, are detailed in Table 2 and Figure 3A. The pain VAS differed significantly among the three groups on PODs 0, 1, 2, 3, 5, and 7 (P<0.001, P<0.001, P<0.001, P<0.001, P<0.001, and P=0.001, respectively). Post-hoc analysis showed significantly lower scores in the 4QTAP block group compared to the LWI group at PODs 0, 1, 2, 3, 5, and 7 (P<0.001, P<0.001, P<0.001, P<0.001, P<0.001, and P=0.006, respectively). Similarly, the NETOIMS group exhibited a significant reduction in pain scores versus the LWI group at these time points (P<0.001, P<0.001, P<0.001, P<0.001, P<0.001, and P=0.002, respectively). Notably, while scores in the LWI group remained above 5 until POD 5, both the 4QTAP block and NETOIMS groups consistently registered scores under VAS 4 without remarkable score rebounds. Additionally, no significant differences were observed between the 4QTAP block and NETOIMS groups at any evaluated time point.

Figure 3 Postoperative pain score, gait speed and peak cough flow. Values are mean ± standard deviation. The postoperative pain score (A) is plotted using visual analogue scale. The percentages of gait speed (B) and peak cough flow (C) are referenced against the values recorded on POD −1 (the day before the surgery, baseline). *(green), P<0.05, 4QTAP compared with the LWI group; *(blue), P<0.05, NETOIMS compared with the LWI group. LWI, local wound infiltration; 4QTAP, four-quadrant transversus abdominis plane; NETOIMS, needle electrical twitch obtaining intramuscular electrical stimulation; POD, postoperative day.

Cumulative opioid consumption, MME, significantly varied among the three groups up to POD 3 (P<0.001, Table 2). The MME (mean ± SD, mg) up to POD 3 in the 4QTAP block (289.8±76.9 mg, P=0.002) and the NETOIMS groups (274.4±98.6 mg, P<0.001) was significantly lower than the LWI group (381.8±85.5), while MME of both 4QTAP block and NETOIMS groups were comparable (95% CI: 231.8–317.1). Similarly, cumulative ibuprofen consumption up to POD 3 also differed significantly among the groups (P=0.004, Table 2). Post-hoc analysis revealed that the cumulative ibuprofen consumption was significantly lower in the 4QTAP block group {mean [interquartile range], 95% CI: 2,800 [4,400], 1,345.1–3,141.9 mg, P=0.007} and NETOIMS group {2,800 [4,400], 1,459.0–3.271.4 mg, P=0.01} than in LWI group {4,400 [400] mg}, while the consumptions of NETOIMS group {2,800 [4,400], 1,459.0–3,271.4 mg} is comparable to the 4QTAP block group.

The incidence of nausea (P=0.57) and vomiting (P=0.87) during hospitalization did not differ among the three groups.

Postoperative function: gait speed and PCF

Gait speed among the three groups improved over time, as depicted in Table 3, with the NETOIMS group exhibiting the earliest improvement trend in gait speed (Figure 3B). Particularly on POD 2, compared to the LWI group, those who experienced a substantial gait speed reduction of over 50% (mean ± SD, 49.2%±21.9%), both the 4QTAP block group (69.9%±17.7%, P=0.008) and the NETOIMS group (75.9%±25.9%, P<0.001) both exhibited significantly higher gait speeds. Nevertheless, the gait speeds of the 4QTAP block and NETOIMS groups were similar to each other (95% CI: 64.7–87.1%, P>0.99).

The NETOIMS and 4QTAP block groups exhibited an earlier recovery trend in PCF compared to the LWI group, as illustrated in Figure 3C. On POD 2, significant differences in PCF among the three groups were observed (P=0.008; Table 3 and Figure 3C). At this time point, post-hoc analysis indicated that PCF (mean ± SD, %) of the 4QTAP block group (70.2%±27.6%, P=0.02) and the NETOIMS group (69.8%±19.9%, P=0.02) was significantly higher than that of the LWI group (51.9%±15.6%). Meanwhile, the PCF values for the 4QTAP block and NETOIMS groups were comparable (95% CI: 61.2–78.5%, P>0.99).

Discussion

In this prospective, single-blinded, randomized controlled trial, either 4QTAP block or NETOIMS was effective in reducing patient-reported pain scores, as well as the requirement of opioids and non-steroidal anti-inflammatory drugs (NSAIDs) up to POD 3 in patients undergoing open PD, compared to LWI. These reduced pain scores were maintained significantly lower for up to a week postoperatively. Additionally, on POD 2, significant improvements in gait speed and coughing ability were observed with the use of 4QTAP block or NETOIMS, compared to LWI.

Continuous LWI can control postoperative pain by blocking pain transmission from nociceptive afferent nerves at the wound surface and by inhibiting local inflammation that sensitizes nociceptors (15). However, the catheters may themselves cause discomfort, and the issues such as dislodgement, blockage, or accidental removal can impede the effective delivery of local anesthetics (16). Moreover, concerns exist about disrupted wound healing due to the anti-inflammatory properties of local anesthetics (17). In addition, LWI’s effectiveness in extensive abdominal surgery, particularly, has been met with skepticism (18). While our study did not compare LWI’s superiority to the absence of any analgesia, our findings show limited benefits from LWI in patients undergoing open PD. This suggests that LWI might not be the best option for procedural analgesia within ERAS pathways, often used empirically despite insufficient evidence.

The superiority of the 4QTAP block compared to LWI in this study can be attributed to its wider coverage of the abdominal area, affecting the skin, muscle, and parietal peritoneum of the abdominal wall (13). A key advantage of the 4QTAP block is its pre-incisional application, facilitating pre-emptive analgesia which helps prevent peripheral and central sensitization, a critical mechanism of postoperative pain control (19). This is evidenced by the reduced need for intraoperative remifentanil and lesser increases in heart rate and blood pressure during skin incision in patients receiving the 4QTAP block. Similarly, NETOIMS demonstrated superior analgesia compared to LWI.

When muscles shorten between their origin and insertion for any reason, functional restrictions occur. Stretching these shortened muscles generates tensile force, which can cause somatic pain or limit the range of motion. In open PD, extensive muscle retraction and prolonged abdominal contraction result in direct tissue damage, causing local edema and microvasculature damage, as well as muscle shortening. This sequence of events increases intramuscular pressure, subsequently leading to reduced local blood flow. As a result, inflammatory cytokines accumulate, triggering C-fiber activation and resulting in pain perception. NETOIMS potentially reduces somatic pain by targeting deep motor endplate zones of skeletal muscles, relaxing contracted muscles, and modulating local circulation and inflammatory cytokine levels (14,20). Notably, pain scores on POD 3, the primary endpoint of the present study, for patients who received NETOIMS (mean ± SD; 2.6±0.8, n=23) were similar to those in a previous study or patients who received a combination of NETOIMS and LWI (3.2±1.5, n=18) (10).

The different functional recovery endpoints assessed in the present study hold significant clinical importance for patients undergoing major abdominal surgery. Gait speed, a key component of the ERAS pathway and an indicator of ambulatory capability, is closely linked to the risk of falls (21). Moreover, effective cough, often impaired postoperatively, is crucial in preventing pulmonary complications, and PCF serves as a measure of cough effectiveness (22,23). Enhanced analgesia resulting from either the 4QTAP block or NETOIMS likely led to improvements in gait speed and PCF during the immediate postoperative period. The reduced postoperative opioid use observed in this study may also have accelerated functional recovery (24). In addition, the muscle-relaxing effect of NETOIMS could enhance the torque during muscle contraction, potentially leading to improvements in walking and coughing abilities (14,25). Epidural analgesia, often heralded as the gold standard for postoperative pain control in abdominal surgeries, is prized for its effectiveness in pain management and promotion of early mobilization (26). Yet, it is not without complications, including hypotension, urinary retention, and delayed bowel function, in addition to its technical complexity and specific contraindications (26-28). In this context, the 4QTAP block and NETOIMS offer a targeted approach to analgesia with fewer systemic effects, positioning them as potential alternatives to epidural analgesia. Notably, their straightforward administration and reduced need for specialized monitoring render these modalities particularly appealing within ERAS protocols. The selection of an analgesic approach for patients undergoing open PD must be guided by a spectrum of clinical considerations, encompassing the proficiency of the healthcare provider and resource accessibility. A comprehensive comparative study is imperative to rigorously evaluate the present modalities against epidural analgesia, necessitating an extensive and detailed investigation.

A key strength of this current study is that it is the first to demonstrate the superior analgesic efficacy of either 4QTAP block or NETOIMS over LWI in major laparotomy surgery. Given that the different mechanisms of the 4QTAP block and NETOIMS are likely to provide synergistic benefits without causing toxic effects, their combined use could be considered for future applications in major laparotomy surgeries. Additionally, the absence of patient discomfort associated with either 4QTAP block or NETOIMS during general anesthesia represents a notable advantage.

This study has several limitations. Firstly, in assessing postoperative analgesic requirements, an important endpoint for evaluating pain relief efficacy, the study involved two distinct medication types, opioids and NSAIDs, presenting challenges in quantification and integration. Secondly, the absence of a sham block or placebo wound catheter with an infusion pump meant that participants were aware of their group assignment, potentially introducing bias. Consequently, the influence of patients’ awareness of their analgesic treatment cannot be entirely ruled out.

Conclusions

This research demonstrated that compared to LWI, the 4QTAP block and the NETOIMS, when combined with multimodal medical analgesia, resulted in enhanced analgesia and expedited functional recovery, as evidenced by improved ambulation and more effective coughing, after open PD. These research findings could lay the groundwork for incorporating 4QTAP block or NETOIMS into ERAS pathways for patients undergoing open PD.

Acknowledgments

The authors thank MID (Medical Illustration & Design), as a member of the Medical Research Support Services of Yonsei University College of Medicine, providing excellent support with medical illustration.

Funding: None.

Footnote

Reporting Checklist: The authors have completed the CONSORT reporting checklist. Available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-23-650/rc

Trial Protocol: Available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-23-650/tp

Data Sharing Statement: Available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-23-650/dss

Peer Review File: Available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-23-650/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-23-650/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was performed in accordance with the tenets of the Declaration of Helsinki (as revised in 2013). The study was approved by Institutional Review Board of Gangnam Severance Hospital (No. 3-2020-0471) and written informed consent was obtained from all individual participants.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Ljungqvist O, Scott M, Fearon KC. Enhanced Recovery After Surgery: A Review. JAMA Surg 2017;152:292-8. [Crossref] [PubMed]
2. Xu X, Zheng C, Zhao Y, et al. Enhanced recovery after surgery for pancreaticoduodenectomy: Review of current evidence and trends. Int J Surg 2018;50:79-86. [Crossref] [PubMed]
3. Melloul E, Lassen K, Roulin D, et al. Guidelines for Perioperative Care for Pancreatoduodenectomy: Enhanced Recovery After Surgery (ERAS) Recommendations 2019. World J Surg 2020;44:2056-84. [Crossref] [PubMed]
4. Rafi AN. Abdominal field block: a new approach via the lumbar triangle. Anaesthesia 2001;56:1024-6. [Crossref] [PubMed]
5. Grape S, Kirkham KR, Akiki L, et al. Transversus abdominis plane block versus local anesthetic wound infiltration for optimal analgesia after laparoscopic cholecystectomy: A systematic review and meta-analysis with trial sequential analysis. J Clin Anesth 2021;75:110450. [Crossref] [PubMed]
6. Gustafsson UO, Scott MJ, Hubner M, et al. Guidelines for Perioperative Care in Elective Colorectal Surgery: Enhanced Recovery After Surgery (ERAS®) Society Recommendations: 2018. World J Surg 2019;43:659-95. [Crossref] [PubMed]
7. Stenberg E, Dos Reis Falcão LF, O'Kane M, et al. Guidelines for Perioperative Care in Bariatric Surgery: Enhanced Recovery After Surgery (ERAS) Society Recommendations: A 2021 Update. World J Surg 2022;46:729-51. [Crossref] [PubMed]
8. Yu N, Long X, Lujan-Hernandez JR, et al. Transversus abdominis-plane block versus local anesthetic wound infiltration in lower abdominal surgery: a systematic review and meta-analysis of randomized controlled trials. BMC Anesthesiol 2014;14:121. [Crossref] [PubMed]
9. Riemma G, Schiattarella A, Cianci S, et al. Transversus abdominis plane block versus wound infiltration for post-cesarean section analgesia: A systematic review and meta-analysis of randomized controlled trials. Int J Gynaecol Obstet 2021;153:383-92. [Crossref] [PubMed]
10. Park J, Kim HS, Park JH, et al. Effectiveness of Intramuscular Electrical Stimulation on Postsurgical Nociceptive Pain for Patients Undergoing Open Pancreaticoduodenectomy: A Randomized Clinical Trial. J Am Coll Surg 2020;231:339-50. [Crossref] [PubMed]
11. Schulz KF, Altman DG, Moher D, et al. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ 2010;340:c332. [Crossref] [PubMed]
12. Park JS, Hwang HK, Kim JK, et al. Clinical validation and risk factors for delayed gastric emptying based on the International Study Group of Pancreatic Surgery (ISGPS) Classification. Surgery 2009;146:882-7. [Crossref] [PubMed]
13. Soliz JM, Lipski I, Hancher-Hodges S, et al. Subcostal Transverse Abdominis Plane Block for Acute Pain Management: A Review. Anesth Pain Med 2017;7:e12923. [PubMed]
14. Shin S, Park J, Hong J, et al. Improved gait speed in spastic paraplegia: a new modality. BMJ Support Palliat Care 2020;10:e41. [Crossref] [PubMed]
15. Abigail W, Sanjay B, Maan H. Novel techniques of local anaesthetic infiltration. Continuing Education in Anaesthesia Critical Care & Pain 2011;11:167-71. [Crossref]
16. Schurr MJ, Gordon DB, Pellino TA, et al. Continuous local anesthetic infusion for pain management after outpatient inguinal herniorrhaphy. Surgery 2004;136:761-9. [Crossref] [PubMed]
17. Brower MC, Johnson ME. Adverse effects of local anesthetic infiltration on wound healing. Reg Anesth Pain Med 2003;28:233-40. [Crossref] [PubMed]
18. Dahl JB, Møiniche S. Relief of postoperative pain by local anaesthetic infiltration: efficacy for major abdominal and orthopedic surgery. Pain 2009;143:7-11. [Crossref] [PubMed]
19. Kelly DJ, Ahmad M, Brull SJ. Preemptive analgesia I: physiological pathways and pharmacological modalities. Can J Anaesth 2001;48:1000-10. [Crossref] [PubMed]
20. Moon DH, Park J, Park YG, et al. Intramuscular stimulation as a new modality to control postthoracotomy pain: A randomized clinical trial. J Thorac Cardiovasc Surg 2022;164:1236-45. [Crossref] [PubMed]
21. Imms FJ, Edholm OG. Studies of gait and mobility in the elderly. Age Ageing 1981;10:147-56. [Crossref] [PubMed]
22. Colucci DB, Fiore JF Jr, Paisani DM, et al. Cough impairment and risk of postoperative pulmonary complications after open upper abdominal surgery. Respir Care 2015;60:673-8. [Crossref] [PubMed]
23. Cassidy MR, Rosenkranz P, McCabe K, et al. I COUGH: reducing postoperative pulmonary complications with a multidisciplinary patient care program. JAMA Surg 2013;148:740-5. [Crossref] [PubMed]
24. Benyamin R, Trescot AM, Datta S, et al. Opioid complications and side effects. Pain Physician 2008;11:S105-20. [Crossref] [PubMed]
25. Kim YS, Park YG, Park J, et al. A Novel Treatment of Anconeus Epitrochlearis Muscle-induced Compressive Ulnar Neuropathy: A Case Report. J Korean Assoc EMG Electrodiagn Med 2019;21:109-14.
26. Freise H, Van Aken HK. Risks and benefits of thoracic epidural anaesthesia. Br J Anaesth 2011;107:859-68. [Crossref] [PubMed]
27. Ahn JH, Ahn HJ. Effect of thoracic epidural analgesia on recovery of bowel function after major upper abdominal surgery. J Clin Anesth 2016;34:247-52. [Crossref] [PubMed]
28. Steinbrook RA. Epidural anesthesia and gastrointestinal motility. Anesth Analg 1998;86:837-44. [PubMed]