“Shoulder-tip pain after carbon dioxide pneumoperitoneum – a reality or myth:” Role of subdiaphragmatic instillation of bupivacaine after laparoscopic cholecystectomy

INTRODUCTION

Laparoscopic cholecystectomy is one of the most widely performed surgeries worldwide. It has evolved into an advanced and more commonly performed procedure as compared to its open surgical counterpart, offering benefits such as lesser post-operative pain, faster recovery, shorter hospital stays, and early mobilization.^[1,2]

The various components of pain that a patient feels post-laparoscopic cholecystectomy have been identified undoubtedly as incisional (somatic pain component), deep abdominal (visceral pain component), and shoulder-tip (referred pain component), with a propensity for visceral component getting transformed into a chronic pain situation.^[3]

The nature and intensity of pain may vary in factors such as duration, location and a pronounced subjective variability, thus making it largely unpredictable.^[4] Several studies have sought to identify methods for reducing the incidence and severity of post-operative laparoscopic cholecystectomy pain.^[2-4]

Besides other causes, such as sub-diaphragmatic fiber stretching, trauma to the abdominal wall nerves at the port site, biliary leakage, and high-pressure insufflation for the creation of pneumoperitoneum,^[5-7] the most prominent cause leading to shoulder tip pain is based on the hypothesis of residual gas in the abdomen causing diaphragmatic distention and irritation causing referred pain at the C4 dermatome.^[8]

Of all the types of pain mentioned above, the sole incidence of shoulder-tip pain has been reported to be frequently ranging from 30 to 50%.^[9,10]

Multiple therapeutic strategies to manage post-operative shoulder-tip pain have been investigated. These include surgery with low-pressure pneumoperitoneum^[11] and administration of prophylactic intraperitoneal analgesia.^[12] It is likely that a combination of analgesic methods may be more effective in reducing post-operative pain.^[13] One such approach is preemptive analgesia, involving the administration/instillation of local anesthetic agents (LAAs), such as bupivacaine, over the gallbladder fossa and subdiaphragmatic port site. The instillation and infiltration of LAAs are considered standard, safe, and cost-effective practices to tackle post-operative pain.^[14,15]

Various studies have concluded that intraperitoneal administration of LAAs is more effective compared to wound site infiltration, although others have reported conflicting results.^[16,17]

In light of this, we aimed to conduct a study to evaluate the effectiveness of bupivacaine instillation in alleviating shoulder-tip pain following laparoscopic cholecystectomy.

MATERIAL AND METHODS

The study was hospital-based and conducted under the department of anesthesiology and intensive care within the operation theater complex at a tertiary care teaching hospital in northern India. The study employed a prospective, double-blinded, parallel-arm, randomized, controlled trial design.

After receiving authorization from the institutional research and ethics committee vide registration No. ECR/1839/Inst/PB/2023 and registering with the clinical trials registry of India vide Ref No. CTRI/2024/08/072243, patient enrolment was initiated. Included participants presented were uncomplicated symptomatic gallstone disease patients (American Society of Anesthesiologists I-II) with ages ranging from 18 to 60 years, of either gender, intended for elective laparoscopic cholecystectomy under balanced general anesthesia.

Exclusion criteria consisted of pregnant patients, those requiring open cholecystectomy, or those with acute cholecystitis, choledocholithiasis, or cholangitis. In addition, patients with a history of known shoulder pain, shoulder trauma, or shoulder surgery, as well as those with opioid addiction, were excluded from the study.

After obtaining confirmed and written informed consent, patients were transported to the designated operating theater by trained personnel on a trolley.

All patients received the same anesthetic technique of pre-oxygenation, pre-medication, propofol induction, vecuronium-mediated muscle relaxation, endotracheal intubation, and isoflurane maintenance, after standard monitoring of electrocardiography, heart rate, pulse oximetry, non-invasive blood pressure was initiated. Minute ventilation was controlled, and adjustments were made to keep end-tidal carbon dioxide (CO₂) between 30 and 40 mmHg.

During the laparoscopy, abdominal insufflation was performed at a rate of 5 L/min, with the intra-abdominal pressure maintained at 12 mmHg using a CO₂ insufflator.

At the end of the procedure, before the removal of the ports, participants were randomly assigned using a computer-generated randomized numbered table into one of the two groups:

1. Group bupivacaine (BUP) (case) – Patients receiving intraoperative intraperitoneal subdiaphragmatic instillation of 20 cc solution of 0.25% bupivacaine (10 mL of 0.5% bupivacaine (BUP) plain + 10 mL of normal saline (NS) = 20 mL of 0.25% total solution)

2. Group NS (control) – Patients receiving intraoperative intraperitoneal subdiaphragmatic instillation of 20 cc normal saline solution without bupivacaine.

In all patients, port site infiltration with the injection of bupivacaine 0.5% was administrated at the time of wound closure.

A numerical Visual Analog Scale (VAS) was used to assess pain scores, ranging from 0 to 10.

Two site-specific VAS scores were measured:

1. Abdomen site pain (VA)

2. Shoulder tip pain (VS).

VAS for abdominal and shoulder site pain was measured preoperatively during pre-anesthetic check-ups (T0). Following surgery and immediately after shifting to post-anesthesia care unit (PACU) (T1), thereafter VA and VS were measured every 30 min. Hemodynamic changes were monitored for 2 h (T2 – T5) in the PACU. After the patient was shifted to the ward, pain assessment of VA and VS was recorded every 6 h for the 1^st 24 h postoperatively (T6–T9).

As part of the protocol, all patients recording VA and VS >3 post-time-point T2 were administered rescue analgesic, injection of ketorolac 30 mg in 100 mL normal saline over 10–15 min, intravenously. Any patient further complaining of persistent pain for any time point post T5 for a minimal duration of 2 h, labeled as breakthrough pain, provision was made to receive an injection of tramadol 75 mg in 100 mL normal saline + injection ondansetron 4 mg.

Statistical analysis was performed using a 2-tailed t-test and Chi-square analysis; P < 0.05 was considered statistically significant. Kaplan–Meier curves and Log Rank test were used for time-to-event analysis.

Microsoft Excel 2019 was used for data organization and standard calculations. Statistical analysis was performed with the Statistical Package for the Social Sciences (SPSS) version 13.0 (SPSS, Chicago, IL, USA).

RESULTS

Demographics

Figure 1 depicts the CONSORT diagram, showing the process of enrollment and final sample size accumulation. The study included a total of 83 patients undergoing laparoscopic cholecystectomy who were randomly assigned into two groups: Group BUP (n = 41) and Group NS (n = 42) as shown in Table 1.

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Figure 1:

CONSORT diagram showing the distribution of patients according to arms. BUP: Bupivacaine, NS: Normal saline.

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Table 1: Demographic characteristics.

Characteristic	Group BUP (n=41)	Group NS (n=42)	P-value
Age (years, mean±SD)	44.2±11.3	43.8±10.9	0.867
Gender (M/F/O)	13/28/0	12/30/0	0.764
ASA Grade (I/II)	23/18	22/20	0.691

ASA: American Society of Anesthesiologists, SD: Standard deviation, BUP: Bupivacaine, NS: Normal saline, M/F/O: Male/Female/Other

Both groups had a similar mean age (around 44 years), with a predominance of female patients, which aligns with the known higher prevalence of cholelithiasis in women, particularly those in their 40s.^[18]

The lack of significant differences between the groups in these demographic factors enhances the validity of the comparison, ensuring that any observed differences in pain outcomes can be attributed to the treatment intervention rather than baseline characteristics.

Pain score trends

The pain score trends across time (measured by the Numerical VAS) clearly indicated that bupivacaine was more effective than NS in controlling shoulder pain. At all post-operative time points, the shoulder-tip pain scores were significantly lower in the BUP group, suggesting that bupivacaine provided sustained pain relief.

Interestingly, while shoulder-tip pain score trends, as seen in Figure 2, were generally mild in both groups (none with average VAS >0.65), the difference between the case and control was consistently significant (P < 0.001). This highlights bupivacaine’s role in minimizing shoulder-tip pain post-surgery, a phenomenon often attributed to diaphragmatic irritation due to CO₂ insufflation.^[8]

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Figure 2:

Pain score trends. BUP: Bupivacaine, NS: Normal saline, VAS: Visual analog score.

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In contrast, abdominal pain score trends, as seen in Figure 3, showed a similar progression for both groups, with a gradual reduction over time. The lack of significant between-group differences in abdominal pain suggests that factors such as the smaller port-incision site or the effect of CO₂ on the peritoneum, rather than mere analgesic intervention, may be more influential in managing this type of pain.

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Figure 3:

Pain score trends. BUP: Bupivacaine, NS: Normal saline, VAS: Visual analog score.

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The charts demonstrate that both abdominal (VA) and shoulder (VS) pain scores were consistently lower in the bupivacaine group compared to the normal saline group across all time points. The difference was more pronounced for shoulder-tip pain scores.

DISCUSSION

Laparoscopic cholecystectomy is a minimally invasive surgery, offering less post-operative pain with early mobilization and shorter hospital stays compared to open cholecystectomy.^[1,2] However, it is still not evidently pain-exempted, and so perioperative pain management holds considerable clinical importance.^[21,22]

Local administration of LAAs may reduce the risk of sedation, gastrointestinal irritation, or injury, as well as complications such as paralysis, respiratory depression, and allergic reactions, in comparison to the systemic use of analgesics.^[23]

One such LAA frequently employed is bupivacaine, used for both intrabdominal instillation and infiltration post-laparoscopy.^[24,25] This is because of the most leading hypothesis that initiation of early post-surgical shoulder-tip pain, primarily due to the presence of residual gas in the abdomen causing stretching of the diaphragm and irritating the phrenic nerve, leads to referred pain at the C4 dermatome.^[8] The application of bupivacaine may help alleviate this discomfort. This study shows that the instillation of subdiaphragmatic space with 20 mL of 0.25% bupivacaine reduces pain in patients undergoing laparoscopic cholecystectomy.

Over the years, various components of pain that a patient feels after laparoscopic cholecystectomy have been studied and can be identified as visceral, parietal, and shoulder-tip. Visceral pain arises at the site of gall bladder dissection due to inflammation of surrounding tissues and stretching of nerve endings, accounting for most of the discomfort experienced in the early post-operative period.^[26] Parietal/somatic pain results from trauma to the abdominal wall nerves at the port site from incisions and trocar insertions during the procedure.^[27]

Numerous studies have argued the origin of shoulder pain to be multifactorial, with proposed causes including neurapraxia of the phrenic nerve, subdiaphragmatic fiber stretching, biliary leakage, and high-pressure insufflation for the creation of pneumoperitoneum leading to nerve trauma and damage.^[5-7]

Of all the types of pain mentioned, the sole incidence of shoulder-tip pain has been reported to be frequently ranging from 30 to 50%.^[28,29] Contrary to this generalization, the incidence of shoulder tip pain as per our study was 16.8% which is practically minimal which is sufficiently self-evident.

In addition, even patients complaining about shoulder pain had it in very mild severity (mean VAS 0.35 ± 0.6) and did not require any specific active interventions, contrary to Park SJ. reporting shoulder pain VAS of >4^[28] and Li and Li reporting persistent pain even after 24–48 h,^[30] while our study recorded mean VAS of shoulder-tip pain at 0.2 ± 0.2 at 24 h. In addition, the significant shoulder-tip pain reduction in Group BUP during the first few hours postoperatively may be attributed to the localized effects of bupivacaine, which has a terminal half-life of 2–8 h,^[31] providing effective analgesia in the immediate postoperative period but tend to fade away over time. This is to say that a more uniform trend of pain reduction was difficult to maintain.

Both abdominal (VA) and shoulder-tip (VS) pain were consistently lower in the study group compared to the control group at all time points. Some degree of abdominal pain was experienced by all patients over 24 h period; however, significant the incidence of VA was, the intensity of the pain was meager and hence required no urge to administer systemic analgesics like opioids, and manageable by few doses of rescue analgesic. The most common location for this pain was the right upper quadrant, followed by pain at the trocar insertion sites. The lack of significant between-group differences in abdominal pain suggests that factors such as the small incision site or the effect of CO₂ on the peritoneum, rather than mere analgesic intervention, may be more influential in managing this type of pain.

Interestingly, while shoulder-tip pain was generally mild in both groups (none with a VAS >0.65), the difference between the study and control was consistently significant (P < 0.001), highlighting bupivacaine’s role in minimizing shoulder pain post-surgery.

A greater proportion of patients in the control group required rescue analgesia as compared to those in the study group. In actuality, rescue analgesia was predominantly sought for abdominal pain rather than shoulder-tip pain. Bhardwaj et al. also found patients from the control group requiring more number of rescue analgesics, mainly at 4–6 h.^[32] Aside from intraperitoneal instillation, the analgesic methods employed were identical in both groups. This displays the fact that bupivacaine instillation is more effective than normal saline in alleviating abdominal pain and avoids the irrational need for opioids or non-steroidal anti-inflammatory drugs.

The most common post-operative symptom observed was nausea in 12 patients, leading to vomiting in three patients. Apart from this, tachycardia was observed during immediate to early post-operative hours in eight patients, presumably due to sudden anxiety and experience of pain.

The strengths of this study lie in its prospective and randomized design, which compares study and control groups. Furthermore, all surgeries were performed by the surgeons following a consistent technique and similar set of instruments. However, pain is subjective, with vast intellectual variability, largely influenced by each person’s threshold and perception. The VAS simply relies on verbal reports from patients to assess pain. This study suggests that using this approach is a viable means of improving postoperative pain management in laparoscopic surgery.

CONCLUSION

Based on the findings and results from this study, we can safely suggest that the instillation of bupivacaine in the subdiaphragmatic space and gallbladder bed definitely minimizes, if not completely allays, the shoulder-tip and abdominal pain arising in post-operative laparoscopic cholecystectomy procedure and lowers analgesic consumption in the early post-operative period.

Bupivacaine administration through intraperitoneal instillation and infiltration to provide relief from postoperative shoulder-tip and visceral pain has been adopted by various surgeons during the modern era of laparoscopy with successful outcomes. This protocol could be implemented for laparoscopic cholecystectomies to promote faster recovery and shorter hospital stays.

Furthermore, our study reports the incidence of shoulder pain to be merely 16.8%, in contrast to some studies citing 30–60% to even as high as 80%. It may be presumed that these higher figures may be overestimated and exaggerated, suggesting that the projected incidence and severity of shoulder tip pain is more of a “myth than actual reality.”