Laparoscopic surgery (LS) is nowadays broadly acknowledged as a type of operation with minimal invasion and has replaced the traditional laparotomy over time (1). Despite the improvement of patient consent with LS, a large number of patients complain of pains after surgery (2). For this reason, LS is often ascribed to operations in surgery, such as intraperitoneal insufflation of carbon dioxide (co2), leading to peritoneal stretching, diaphragmatic irritation, alterations in intra-abdominal  (power of hydrogen) pH, and containment of the insufflated gas inside the abdominal cavity following the operation (3).
The pain felt by a patient following LS is dividable into three forms: parietal, visceral, and shoulder pain (SP), which differ in intensity. Whereas parietal and visceral pains lessen after twenty four to forty eight hours, SP is probably of greater significance (4). SP is one of the unpleasant postsurgical symptoms (5) that has been found in up to 2/3 of patients (6) and its severity rises constantly in the first three to six hours after surgery, reaching the utmost intensity 12 hours post-operation (7).
In different studies, such as Imbelloni (2014), Kalaivani (2014), and Ko-iam (2016) the frequencies of SP varied from 27 to 80% (8-10). By definition, SP is a sense of pain in the shoulder (11). Following laparoscopic cholecystectomy (LC), SP may represent emotional indications and alterations in vital symptoms, vomiting and nausea.Inpatients with SP, pain may be indicated as nauseous, sharp, deep and boring (5).
Despite this, the severity of postsurgical abdominal and SP is still important, restricting LC as a same-day method in great number of patients (12).
Post-surgical abdominal and SP after LC is the leading causes of anxiety to patients, though with less severity than that of an open method (13).
The precise mechanisms of SP following LS are not known (11). Apparently, they have a multifarious mode of action, but it is mostly theorized to be CO2 gas retention among the hepatic dome and right diaphragm (14). Other suggested reasons are neuropraxia from the phrenic nerve, elevated stretch on the diaphragmatic attachments of the liver, stretching of the subdiaphragmatic fibers due to the pneumoperitoneum, caused by losing visceral surface tension and peritoneal injury of ischemic, chemical, or traumatic hurt (4).
Taş (2013) and Suginami (2013) believe that post-surgical SP is assumed to stem from pneumoperitoneum attained by CO2 insufflation and remaining in the abdomen, thereby inducing peritoneal stretching and irritation of the phrenic nerve and diaphragm , leading to inflicting pain to the shoulder (1, 2).
Cha (2012) states that shoulder tip pain is caused by diaphragmatic stretching with phrenic nerve neuropraxia (6). Singh (2013) denotes that SP following LC happens upon turning CO2 into carbonic acid on the peritoneal surfaces. SP is caused by peritoneal insufflation, particularly with the use of an exaggerated trendelenburg position. Using the trendelenburg position in the long run is a cause of SP as well (11).
In a number of investigations, the relief of shoulder tip pain in laparoscopy has been assessed by various methods (15, 16). The focus of some investigations was on operation practices, pressure, temperature, and moisture of pneumoperitoneum, drainage, and various practices to alleviate the phrenic nerve stimulation (2, 17-19). In other investigations, drugs were administered to evaluate SP prevention (20-25). Alkhamesi (2007) demonstrates that local anesthetic methods are a portion of the multifaceted strategy for postsurgical pain control (15); however, the findings of the investigations require careful examination.
Therefore, postsurgical SP is a typical unwanted consequence following laparoscopic practices because LS is highly prevalent. SP emerges mostly following patient verticalization and may persist even following standard prescription of analgesics (14).
However, various techniques to reduce SP include drainage, pulmonary recruitment maneuver (PRM), preoperative premedication with drugs, drainage, positioning, low-pressure carbon dioxide, instillation of drug and fluid into the peritoneal cavity, acupuncture treatments, neuromuscular blockade, etc. (1,5,6,11,12,26-28); however, several studies with various findings have been conducted in this regard.
Regarding the different results of these interventions in mitigating SP following LS, it is necessary to conduct a meta-analysis that provides abvious and consistent results and suggestions for researchers. Overall, systematic review and meta-analysis are essential tools for summarizing available evidence reliably and accurately.
Thus, this study attempted to identify and assess the interventions used to reduce shoulder pain following LS.
 

Totally, 93 primary articles were retrieved in the initial literature search. Among these, 44 duplicate and irrelevant articles were removed after considering the exclusion and inclusion criteria and finally, 39 full-text articles were systematically reviewed. The flowchart of the study reviews is shown in Figure 1. All studies were randomized clinical trials. The publication years of the studies ranged from 2009 to 2020. Based on existing studies, interventions used to reduce SP following LS according to the surgical phases were included in this study.

Figure 1. PRISMA diagram

Preoperative interventions
The presurgical phase is the period between decision making for operation and the start of the operation practice. In the present study, presurgical interventions involve many components and procedures performed before the patient’s admission to the hospital for a surgical operation to reduce postoperative SP.
Preoperative premedication with a drug: this drug included prescript premedication gabapentin (600 mg, oral) 30 min before surgery (30) and pregabalin (150 mg: 2 capsules of 75 mg), gabapentin (600 mg: 2 capsules of 300 mg), two hours before the beginning of operation (14), clonidine (0.2 mg clonidine HCL, oral) 90 min prior to induction (31), parecoxib (40 mg dissolved in 5 mL of normal saline) by intravenous injection 30 min before the surgery (32),and acetazolamide (5 mg/kg, oral) 1 h before the surgery (33) to prevent postoperative SP after LS.
Intraoperative interventions
The duration of the intraoperative phase is from admitting the patients to the operating room for the surgery until they are relocated to the recovery room. In the present study, intraoperative interventions involve measures andprocedures performed in the operating room during anesthesia and surgery to reduce postoperative SP.
These interventions includeintraperitoneal fluid therapy, an alternative used to reduce SP in LS, such as receiving intraperitoneal lignocaine (10 mL, 2%) versus bupivacaine (10 mL, 0.5%) by diluting every one in 10 mL of normal saline in LC (13), intraperitoneal ropivacaine (20 ml of 0.5%) by spraying 10 mL of solution into the hepato diaphragmatic space, 5 mL into the space within the liver and kidney and 5 mL in the area of the gallbladder (11), intraperitoneal 10 mL of bupivacain 0.5%, (in the space right under the diaphragm in the trendelenburg position) and 0.5 mg/kg of acetazolamide  IV (intravenously) (30), intraperitoneal 50 ml of sodium bicarbonate ((NaHCO3) sodium bicarbonate 7.5% in 1000 ml of normal saline at 37 °C) injected in the surgical bed, superior surface of the liver below the right hemi diaphragm (31), intraperitoneal ketorolac (IP group: 1 mL of intravenous saline + ketorolac 30 mg in 250 mL of normal saline , 2- IV group: IV ketorolac 30 mg in 1 mL+ intraperitoneal normal saline 250 mL ) under standardized anesthesia (32), intraperitoneal instillation of 100 mg hydrocortisone (in 250 mL of normal saline) or 100 mg of bupivacaine (in 250 mL of normal saline) prior to insufflation of CO2 into the peritoneum (33-34), intraperitoneal 20 mL of Bupivacaine 0.25% in the gallbladder bed , abdominal CO2 insufflation during the resection of gallbladder (35), instillition of 20 ml of 0.5% bupivacaine intraperitoneal method at the terminal of laparoscopic surgery (36), intraperitoneal instillation of 100 mg of hydrocortisone in 250 ml of normal saline prior to insufflation of CO2 into the peritoneum (37), intraperitoneal ropivacaine 0.2% (1 ml/kg) instilled into the peritoneum before surgery (38), intrathecal fentanyl (23), and sedative effect of EMLA and trigger point injection (39) for postoperative pain management and relief after LS. 
Another intraoperative intervention was drainage, which included forced evacuation of residual CO2 with the instillation of warm saline (1000-1500 mL) in the abdomen from one of the two supra inguinal ports until it spilled out of the staying open trocars (1), peritoneal gas drain (40), low-pressure CO2 through the pneumoperitoneum using paCO2 of 7–10 and 12–14 mm Hg (41), humidification of carbon dioxide by the HumiGard MR 860 Surgical Humidification System, CO2 insufflation with pressure set to 14 mm Hg, and an over gas flow limit of 6.5 L/min (42) for reducing postoperative SP in LS.
Low vs. Standard Pneumoperitoneum Pressure (43), spinal anesthesia with Subdiaphragmatic injections of 10 mL of 1% lidocaine at the port sites at the starting of the method (25), spinal/epidural block anesthesia (44), inactive-valve release on abdominal distension and active aspiration, (7), peritoneal suction with drainage, inserting Hemovac plastic passive drains in suprapubic position in a way that the opening of the drain was tangent to the peritoneum, without negative pressure for at least 24 h (45), peritoneal  nebulization  of Ropivacaine of ropivacaine 1% during LC (3). Bupivacaine 0.25% (50 mL solution), upivacaine ketamine with a whole volume of 50 mL intraperitoneal instilled solution combined with lung recruitment (46), a combined treatment of intraperitoneal normal saline and the PRM (47) use to reduce postsurgical SP in LS.
Neuromuscular blockade
Low insufflation pressures are plausible with neuromuscular blockade deeply throughout LS to mitigate SP after laparoscopy. In this method, continuous infusion of rocuronium was done after the induction, and titration was made based on the group appointment for maintaining either (PTC) the post-tetanic count at one to two in the deep NMB group, or train-of-4 (TOF) response at one-two in the moderate NMB group. Neuromuscular function was determined at the wrist by an acceleromyograph. This muscle relaxation power was retained by the completion of the abdominal fascia closure (48).
Pulmonary recruitment maneuver (PRM)
Five manual pulmonary inflations were offered at the completion of operation with an uppermost pressure of 60 cm H2O or 40 cm H2O (26, 49), which reduced residual pneunoperitoneum, thus reducing residual CO2 gas resulting in declined irritation of the phrenic nerve and reduction in post-laparoscopic SP.
Postoperative interventions
The extent of postoperative phase is from admitting the patients to the recovery room or PACU (post anesthesia care unit) and the time they are returned back to the operating unit until discharge. In the present study, postoperative interventions involve different measures and procedures after surgery to reduce postoperative SP.
This intervention consists of patients with suction drain positioned in the subhepatic space (28), exaggerated lithotomy position on SP after LC (5), and acupuncture treatments registered according to STRICTA guidelines (50) for pain relief after LS.
The findings of the meta-analysis were reported 6, 12, and 24 hours after LC. The results showed that there was heterogeneity between studies (I2 = 69.7%, P = 0.037, Q = 6.60) 6 hours after the operation in the intervention group.
Therefore, the studies and final results of the effects of the studies were combined using the SMD and random method. The results of the intraoperative intervention show that the mean VAS score is 1.46 with CI 95%: (-0.32, 3.24) in intervention group 6 hours after surgery.
There were homogeneity among studies (I2 = 1.5%, P = 0.362, Q = 2.03) in the control group 6 hours after operation. Therefore, studies and final results of the studies were combined using a fixed effects model. The estimated mean VAS score in the control group is 1.87 with CI 95%: (0.79, 2.94) at 6 hours post-operation. The VAS score of control group is greater than that of intervention group at 6 h after surgery (Figures 2 and 3).

 
Figure 2. Forest plot of Visual Analog Scale score in the intervention group 6 h post-operation
 
 
Figure 3. Forest plot of Visual Analogs Scale score in the control group 6 h post-operation

There was homogeneity between studies based on the finding of this meta-analysis 12 h post-operation in the intervention group (I2 = 0, P = 0.57, Q = 1.12). Thus, the results were combined according to the type of data obtained from the fixed effects model. These results demonstrated that the average of VAS score in intervention group was 2.06 with CI 95%: (0.91, 3.20) 12 h post-operation.
There was no homogeneity between studies in the control group at 12 hours post-operation (I2 = 62%, P = 0.072, Q = 5.27). Hence, the results were combined according to the type of data obtained from the random effects model. The results demonstrated that mean VAS score in the control group was 2.35 with CI 95%: (0.571, 4.13). The VAS score of the intervention group was lower than that of the control group 12 hours following surgery (Figures 4 and 5).

 
Figure 4. Forest plot of Visual Analog Scale score in the intervention group 12 h post-surgery
 
 
Figure 5. Forest plot of Visual Analog Scale score in the control group 12 h post-operation

Based on the finding of meta-analysis in the intervention group (I2 = 0, P = 0.83, Q = 0.88) 24 hours post-operation, there was homogeneity between studies. Therefore, the results were combined according to the type of data obtained from the fixed effects model. The results of intraoperative intervention show that the average VAS score in the intervention group is 0.96 with CI 95%: (-0.21, 2.13) 24 hours post-operation.
In the control group within twenty four hours after operation (I2=20%, P = 0.29, Q = 3.75), there was homogeneity between studies. Hence, the results were combined according to the type of data obtained from the fixed mod el. The average VAS score twenty four hours post-operation in the control group is 1.27 with CI 95%: (0.33, 2.21), which is higher than that of the intervention group at 24 hours after operation. Table 1 indicates articles included in present systematic review in detail.

Discussion

In this systematic review and meta-analysis evaluated interventions reduced SP following LS. The results of articles included in this systematic review showed that preoperative (e.g., gabapentin, clonidine, parecoxib, and acetazolamide) (14, 51-53), intraoperative (e.g., intraperitoneal ropivacaine, lignocaine, and ketorolac) (6, 11, 13, 30), and postoperative (e.g., suction drain placed in the subhepatic space and acupuncture treatments) (28, 50) interventions significantly mitigated SP after laparoscopy.
The reviewed investigations showed that the residue of CO2 gas following LC could persist in peritoneal space for a duration of 24 h post-operation. Therefore, a high percentage of patients would experience SP after LS due to CO2, which will significantly affect gastrointestinal symptoms, such as nausea and vomiting, postoperative activity, and patient satisfaction with LS (49).
Among the studies that were analyzed in this meta-analysis, those of Amini (2014) and Sarvestani (2013) examined the influence of intraperitoneal hydrocortisone alone with bupivacaine on postsurgical pain of LC (33،37).
Sarvestani (2013) provided standard anesthesia and randomly injected 250 ml of NS (normal saline) or 100 mg of hydrocortisone in 250 ml of NS (normal saline) in the peritoneum before injecting carbon dioxide into patients. Abdominal pain and SP scores were notably lower in hydrocortisone group in the PACU (recovery room) six, twelve, and 24 hours after operation. These results showed that intraperitoneally injected hydrocortisone reduced pain after (LC) with no considerable unwanted consequences (37). Amini (2014) in his study treated the patients with standard anesthesia and randomly injected themwith100 mg of hydrocortisone in 250 ml of NS or a hundred mg of bupivacaine in 250 ml of NS in peritoneum before CO2 injection. Patients were then evaluated for postoperative analgesia, nausea, and vomiting. The result showed that intraperitoneally administered hydrocortisone and bupivacaine before the penetration of CO2 gas could reduce postoperative pain and the need for analgesia. No postoperative side effects were observed in LC (33).
Several methods have been reported for the decrease of post-laparoscopic pain by intraperitoneal injection of hydrocortisone, bupivacaine and other drugs. These include received intraperitoneal lignocaine (10 mL 2%) versus bupivacaine (10 mL 0.5%) by diluting one in 10 mL of normal saline (13), intraperitoneal infusion of 100 mg hydrocortisone plus and 100 mg bupivacaine (in 250 ml of NS) or  20 mL bupivacaine 0.25% in gallbladder bed during abdominal CO2 insufflation and resection of gallbladder (34), intraperitoneal instillation of 100 mg bupivacaine (in 250 ml of NS)  (35), instillation of 20 ml 0.5% bupivacaine intraperitoneal method (36), intraperitoneal ropivacaine 0.2% (1 ml/kg) instilled into the peritoneum (38).
Another study included in the meta-analysis was that of Haghgoo (2016) who used peritoneal suction drainage to reduce SP in gynecological laparoscopy. The researchersdivided the patients randomly into two groups, one with drainage and the other without drainage. In all patients, the abdominal cavity was washed with 1.5 L of warm saline at the completion of the operation. For patients whose abdomens were closed by drainage, the hemovac plastic inactive drains were placed in suprapubic position. The opening of drains was tangential to the peritoneum and without pressure. The drains were placed at least for 24 h (45). Drainage in the peritoneal cavity is believed to reduce postoperative pain by removing CO2 gas. Some other studies reported that the use of drainage reduced the overall pain after surgery. However, the study of Georgiou (2011) showed that patients with drainage and those without drainage were not significantly different after cholecystectomy (57).
PRM is one of the methods for the evacuation of CO2 gas from the abdominal cavity in LS. This mechanism reduces the intensity of SP and so reduces PCA (patient-controlled analgesia) an alternative to palliate SP after surgery (2).
A study by Ryu (2017) showed that PRM significantly reduced residual pneunoperitoneum, thus a reduction in residual CO2 gas resulted in declined botheration of the phrenic nerve and consequently reduced PLSP (49). Finding of a research by Khanna (2013) revealed that PRM caused pulmonary edema in pressure between forty and sixty cm of water, increased lung volume, and decreased diaphragm, resulting in the remaining discharge of CO2 from the abdominal cavity, thus reducing patients' postoperative SP (58). Sharami (2010) performed PRM with pressure 40 cm of water at terminal of LS and noticed a considerable reduction in intensity of SP in patients four, twelve, twenty four, and forty eight hours after operation (59).
According to finding of this meta-analysis, the use of PRM by Pergialiotis (2015) seemed to be a simply executed procedure with the potential prevention of post-laparoscopic SP (60).
Various pharmacological and mechanical methods have been utilized to palliate SP after LS. In an investigation included in the meta-analysis, Ghezzi (2011) compared SP in patients after laparoscopic hysterectomy (LH) versus mini laparoscopic hysterectomy (MLH). In this study, patients underwent LS with 5 mm ports (LH) or a needle approach using 3 mm tools (mini MLH). The size of the ports could be diminished with confidence without adversely affecting the surgeon's capability to accomplish LH. The mentioned research indicated that the reduced size of the ports led to no significant decrease in postsurgical pain and receiving analgesia in patients with LH (56). However, some articles, like Novitsky (2005), Huang (2003) and Lau (2005) reported that postoperative pain was less than LC in mini laparoscopy (61-63).
Another study included in meta-analysis was conducted by Herrmann (2015), who examined the effect of insufflation with humidified and heated carbon dioxide on pain after laparoscopic vaginal hysterectomy. All patients were administered standard anesthesia and then randomized for a case group of pneumoperitoneum with cold CO2 (room temperature), dry (0% humidity), and for an intervention group of warm CO2 (35 ± 2 °C), and wet (98% humidity) CO2. For CO2 infiltration, the pressure was set to 14 mm Hg and a high gas flow was limited to 6.5 L per minute. The finding of the research demonstrated that the penetration of hot and humid CO2 significantly reduced SP, particularly in the initial 6 h post-operation, as well as the need for morphine (42). However, studies by Yu (2013) and Sammour  (2010) on effect of hot and humid CO2 gas on short-term intraoperative and postoperative consequences showed that postoperative pain scores have equivalent postoperative recovery parameters in both intervention and control groups (64, 65).

 

Limitations

The limitation of this study is the inclusion of publications only from ISI Web of Science, PubMed, MEDLINE, Cochrane, ProQuest, Scopus, Google Scholar, and Scientific Islamic Database (SID); databases from 2009-2020, and other articles in other databases were not included.

 

Conclusion

Our findings showed that patients experience SP after LC. This pain will also have a significant effect on the occurrence of gastrointestinal symptoms, such as nausea and vomiting, the patients’ postoperative activity and especially their satisfaction with LS. However, studies with the intervention of accelerated CO2 gas excretion from the abdominal cavity revealed that both SP after laparoscopy and the need for analgesia were significantly reduced in patients. In addition to relieving SP and reducing analgesia, these interventions reduced nausea in patients of the intervention group. Therefore, it can be concluded that the administration of pharmacological or and none pharmacological interventions to reduce SP in LS will accelerate postoperative activity, recovery, and satisfaction of patients, in addition to the relief of pain.

 

Acknowledgements

The authors are grateful to Sabzevar University of Medical Sciences, non-communicable disease center.
This article is derived from a research approved by Sabzevar University of Medical Sciences with the code 99001 and ethics code: IR.MEDSAB.REC.1399.031

 

Conflicts of Interest

We declare no conflict of interest regarding this manuscript.

 

Funding

None.