Categorical variables were compared with the chi-square test or Kruskal–Wallis test. The total volumes of postoperative residual carbon dioxide gas were significantly different between the 1- and 2-port groups and between the 1- and 3-port groups . The volume of residual gas and the time to the first passage of gas were positively correlated. The total volume of residual gas was more strongly correlated with the operative wound pain score than with the shoulder pain score. Additionally, the pre- and postoperative white blood cell counts, postoperative hospitalization duration, residual carbon dioxide volume, and shoulder pain score were significantly different between patients with and without a drainage tube. Although the volume of residual gas was not correlated with the shoulder pain score, the author found that both were lower in patients with a drainage tube than in those without, indicating that a drainage tube could be safely used to decrease residual gas volume and the shoulder pain score without increasing the risk of postoperative infection.Free residual gas after laparoscopy may cause shoulder pain, decreasing patient satisfaction with the procedure. We analyzed the correlation between postoperative residual carbon dioxide gas and shoulder pain, explored the peri- and postoperative factors associated with residual carbon dioxide and determined the effects of the use of a drainage tube. A cohort of 326 patients who underwent laparoscopic adnexal surgery between March 2005 and June 2018 at a teaching hospital in Korea was retrospectively analyzed through a medical records review. The enrolled patients were divided into 1-, 2-, and 3-port groups. The right volume, left volume, and total volume of residual gas were calculated using a formula based on measurements obtained from chest X-rays. Continuous variables were compared using Student  Postoperative residual carbon dioxide gas tends to accumulate below the diaphragm and around the liver and stomach due to the density of gas and the effects of gravity. Free residual carbon dioxide gas is thought to cause shoulder pain and upper abdominal pain in patients by irritating the phrenic nerve. However, the causes of postoperative shoulder pain are unknown, and the correlation between the amount of free air and shoulder pain is also uncertain. Some authors reported that all patients began to get out of bed on the first day (12–24 hours) after surgery. Most of the patients began to have shoulder pain after getting out of bed for the first time. It may be that the location of gas accumulation in the abdominal cavity changes with body position and then causes shoulder pain. Although the definite cause of shoulder pain after laparoscopy is unknown, free gas after laparoscopy in the abdominal cavity is suggested to be correlated with shoulder pain. With this, some authors have tried to decrease shoulder pain in patients with suction drains or low flow rates to induce pneumoperitoneum followed by high flow rates.–5To perform laparoscopy, pneumoperitoneum must be induced by inserting carbon dioxide gas into the peritoneal cavity. Although many surgeons attempt to remove residual carbon dioxide gas from the peritoneal cavity after laparoscopic procedures, postoperatively, a large volume of residual carbon dioxide remains as free gas.,6–8 Because most patients think shoulder pain has nothing to do with surgery, it makes them more anxious. This may lead to discomfort and poor quality of life after laparoscopic surgery and greatly reduce patient satisfaction.Many surgeons neglect to remove free residual gas because the shoulder pain it causes tends to resolve spontaneously within several days. Some patients who undergo laparoscopy complain that they have more shoulder pain than operative wound pain, and this pain may decrease a patient’s satisfaction with the procedure. Aside from its cosmetic merit, patients who undergo 1-port laparoscopy have shown similar levels of postoperative shoulder pain to those treated with conventional laparoscopy.,10 The factors that cause shoulder pain and the perioperative and postoperative factors associated with shoulder pain or residual gas need to be explored.Recently, advancements in minimally invasive procedures have allowed 1-port laparoscopy to be performed in many hospitals. Single-port laparoscopy has some merits, including better cosmetic results, because these surgical procedures leave only 1 operative wound scar in the umbilicus.The author therefore sought to analyze the correlation between the volume of postoperative residual carbon dioxide gas and postoperative shoulder pain and explore the perioperative and postoperative factors associated with the 2. The correlation between postoperative pain and postoperative shoulder pain after laparoscopy was assessed to explore the cause of shoulder pain. Additionally, the author suggests a strategy for decreasing the volume of residual carbon dioxide gas.A retrospective cohort study was performed via a review of the medical records and radiological studies related to patients who underwent laparoscopic adnexal surgery at a teaching hospital in Korea between March 2005 and June 2018. This study was approved by the institutional review board of our hospital (GNAH2017-09-001). Of the 358 patients who underwent laparoscopy for adnexal surgery during the study period, 326 were enrolled, and 32 patients were excluded for not having undergone a postoperative chest X-ray examination, as it is not a standard procedure and is performed only if the patient experiences shoulder pain or respiratory symptoms. Because many patients who underwent laparoscopy had complaints of shoulder pain or dyspnea, chest X-rays in the upright position were examined in the radiology room for residual carbon dioxide or other lung lesions on postoperative day 2. Because this was a retrospective cohort study, patients who did not undergo chest X-ray were excluded from this study because the residual carbon dioxide volume was calculated from chest X-ray.The enrolled patients were a consecutive case group and divided into 3 study groups according to the number of ports used into the 1-port (198 patients), 2-port (114 patients), and 3-port (14 patients) groups  was inserted into the uterine cavity, except in young patients with no history of coitus.Patients were admitted the day before surgery, and consent for treatment was obtained from all patients. The possibility of conversion to laparotomy in cases of severe adhesion, malignancy, or inadequate visualization of the operative field was explained. A Fleet enema was administered at 7:00 Because a single surgeon performed the procedures for all patients enrolled in this study, the surgical procedures were performed using the same methods. A small longitudinal skin incision was made in the umbilicus, and a Veress needle was inserted to establish pneumoperitoneum. A 10-mm trocar was then placed in the umbilical area, and a 10-mm, 0° laparoscope was inserted through the trocar. The pelvic anatomy was carefully inspected to determine whether conversion to laparotomy was necessary.In 1-port laparoscopic surgeries, 3 trocars (two 12-mm trocars and one 5-mm trocar) were inserted into separate fingers of a surgical glove and secured with rubber bands. The wrist portion of the glove covered the wound retractor, and 3 Babcock clamps were placed on the edges of the retractor to prevent carbon dioxide leakage. A 10-mm laparoscope and atraumatic forceps were inserted through the umbilical multichannel port.® wound retractor  was placed in the umbilical incision. Two 12-mm trocars were inserted into separate fingers of a No. 6 surgical glove and secured with rubber bands, and the other 3 fingers of the glove were tied together.In 2-port laparoscopic surgeries, an ancillary 5-mm trocar was placed low in the left abdomen under laparoscopy. The umbilical trocar was removed, and the skin incision was extended to approximately 1.5 cm, which is sufficiently wide to allow passage of an index finger. The skin incision was extended to the upper and lower margins of the umbilicus to minimize abdominal scarring. An extrasmall AlexisAncillary 12-, 10-, or 5-mm trocars were inserted low in the right and left abdomen under laparoscopic observation. In the conventional laparoscopy group, the ancillary port site low in the abdomen was extended to remove surgical specimens, if necessary. A wound retractor was not used in the 3-port laparoscopic procedure.®, Sejong Medical, Co., Ltd., Korea) was placed through the left 5-mm port site if inflammation, adhesion, or hemorrhage was evident, and the abdominal wounds were sutured.The pelvic masses were primarily ovarian cysts and tumors. The procedures performed included adnexectomy, cystectomy, and myomectomy in 1 case where a pedunculated subserosal myoma had been initially diagnosed as an adnexal mass. A Jackson–Pratt-style drainage tube  counts, change in the hemoglobin (Hb) level, time to the first passage of gas, postoperative hospitalization duration, postoperative shoulder pain score and operative wound pain score, were investigated. Usually, in our hospital, the postoperative pain score assessment has been included in postoperative nursing care. With this, all postoperative patients were assessed for postoperative shoulder and operative wound pain scores according to a verbal rating scale  every 4 hours for a total of 10 times or more. However, missing pain scores were analyzed as a missed value. to calculate the volumes with the respective formulas. The calculated volumes of residual gas on the right and left sides were added together to obtain the total volume of residual carbon dioxide gas.The volume of residual carbon dioxide gas was measured as the right volume, the left volume, and the total volume of residual gas using a formula that incorporated measurements obtained on chest X-ray Fig. . On ches® statistical software . Continuous variables were compared using Student t test. Categorical variables were compared with the chi-square or Kruskal–Wallis test. All tests were 2-sided, and a P value of ≤.05 was regarded as significant.The results were analyzed using SPSSAnalysis of the clinical characteristics in the 1-, 2-, and 3-port groups showed that the mean patient ages were 34.6 ± 12.1, 35.4 ± 12.4, and 29.6 ± 10.2 years, respectively. There were no significant differences in the mean patient age among the study groups. In the 1-, 2-, and 3-port groups, the mean parity was 1.1 ± 1.2, 1.0 ± 1.1, and 0.4 ± 0.8, respectively, with no significant differences among the groups. There were also no significant differences in height, body weight, or body mass index (BMI) among the study groups , the 1- and 3-port groups (6869.2 ± 1804.5 vs 5421.4 ± 1678.0 cells/µL), and the 2- and 3-port groups (6678.1 ± 2288.9 vs 5421.4 ± 1678.0 cells/µL). The change in Hb level was significantly different between the 1- and 3-port groups and between the 2- and 3-port groups . The postoperative hospitalization duration was significantly different between the 1- and 2-port groups, the 2- and 3-port groups, and the 1- and 3-port groups .The total volume of postoperative residual carbon dioxide gas was significantly different between the 1- and 2-port groups and the 1- and 3-port groups . However, the difference between the 2- and 3-port groups was not significant.There were correlations between the total volume of postoperative residual carbon dioxide and weight, BMI, and port number, with heavier and more obese patients having more residual carbon dioxide gas and patients in whom more ports were used having less residual carbon dioxide gas.With respect to the number of ports used, there was no difference in the postoperative volume of residual carbon dioxide gas between the 2- and 3-port groups. A drainage tube was used in all patients treated with 2-port and 3-port laparoscopy and played a major role in decreasing the volume of postoperative residual carbon dioxide gas.There was no correlation between the total volume of postoperative residual carbon dioxide and operation time Table . The volP = .048; −0.140, .015; −0.185, .001; −0.218, .000; −0.163, .005; −0.231, .000; −0.217, .000; and −0.230, .000, respectively). However, the total volume of residual carbon dioxide was correlated only with a shoulder pain score of 2 . The postoperative shoulder pain scores were analyzed to determine the correlation with operative wound pain scores. The postoperative shoulder pain scores were not correlated with the operative wound pain scores except for the pain score of 10 . With this, postoperative wound pain and postoperative shoulder pain may have other causes.The postoperative shoulder and operative wound pain scores were assessed according to a VRS (pain scores: 0–10) every 4 hours for a total of 10 times. The pain score was routinely assessed for all postoperative patients in my clinic. The pain scores were analyzed to determine their correlations with the total volume of residual carbon dioxide gas. The total volume of residual carbon dioxide gas was correlated with operative wound pain scores of 3, 4, 5, 6, 7, 8, 9, and 10  resulted in a lower incidence of shoulder pain after laparoscopic hysterectomy than moderate neuromuscular blockage and standard-pressure pneumoperitoneum (12 mm Hg). In a retrospective case cross-sectional study, abdominal compression and pulmonary recruitment maneuvers after transvaginal natural orifice transluminal endoscopic surgery (vNOTES) might be considered to decrease postlaparoscopic shoulder pain. In a meta-analysis of randomized controlled trials, the authors concluded that a pulmonary recruitment maneuver with 40 cm H2O performed either alone or accompanied by intraperitoneal saline was a promising intervention for alleviating shoulder pain within 48 hours following gynecologic laparoscopy. With these articles, it was suggested that free pneumoperitoneum is the cause of postoperative shoulder pain and that methods to decrease free air were a strategy for postoperative shoulder pain.To decrease postoperative shoulder pain, some authors have used deep neuromuscular blockade and low-pressure pneumoperitoneum. investigated whether active suction decreases residual intraperitoneal gas and whether residual gas decreases pain scores. They performed a prospective randomized controlled study to investigate whether active gas suction reduces the intraperitoneal residual carbon dioxide volume and analyzed the effect of active gas suction on postoperative pain after laparoscopic cholecystectomy. They found that active suction significantly decreased the residual intraperitoneal gas volume and postoperative pain after laparoscopic surgery. In another randomized controlled study, the effect of active gas aspiration on postoperative shoulder pain relief after diagnostic laparoscopy was significantly superior to that of simple gas evacuation and was not associated with any adverse events. In our study, although the shoulder pain score was not correlated with the volume of residual carbon dioxide, a drainage tube may play a similar role in decreasing the volume of residual carbon dioxide gas. However, the abdominal pain score was correlated with the volume of residual carbon dioxide. Although the shoulder pain score is a subjective parameter, the correlation between the residual gas volume and the shoulder pain score has been supported by clinical studies.A study of 20 patients who underwent gynecological laparoscopic surgery revealed a correlation between the residual intraperitoneal gas volume and pain scores. Pain scores are subjective parameters, while the volume of residual intraperitoneal air is more objective. Lee et al who suggested that it may be useful for preventing postoperative shoulder pain among patients undergoing gynecological laparoscopic surgery and could decrease the need for pain medication. In contrast, Kandil and El Hefnawy suggested that the origin of pain after laparoscopic cholecystectomy is multifactorial. Because patients with and without drainage tubes have a similar incidence of postoperative shoulder pain, drains should not be used with the intention of preventing shoulder pain. In a prospective randomized study, the authors suggested that prophylactic surgical drainage may not be necessary to prevent postoperative morbidity after laparoscopically assisted vaginal hysterectomy. In a meta-analysis, abdominal pain 24 hours after surgery was less severe in the no-drain group. No significant difference was present with respect to the presence and quantity of subhepatic fluid collection, shoulder tip pain, parenteral ketorolac consumption, nausea, vomiting, or hospital stay. With this, the authors concluded that the study was unable to prove that drains were useful in reducing complications in laparoscopic cholecystectomy.Drainage for peritoneal suction was investigated by Haghoo et al,However, drains still play a role in gynecological laparoscopy in select women, such as those with persistent discharge from raw surfaces, bowel injury, or frank pus in the abdomen. In our study, the use of a drainage tube decreased the volume of residual carbon dioxide gas and had no adverse effects on postoperative inflammation. Because there was a greater incidence of inflammatory disease among patients with a drainage tube, such as tubo-ovarian abscesses or pelvic inflammatory diseases, the preoperative WBC count was higher in patients with a drainage tube than in patients without. Although the postoperative WBC count was not significantly different between these groups, it was lower in patients with a drainage tube, suggesting an improvement in inflammation after the operation and antibiotic treatment.Our study has certain limitations. First, postoperative shoulder and abdominal pain were evaluated using a pain score based on a VRS. Because the pain score is a subjective parameter, it has limited value in providing an objective quantification of pain. It is possible that the low correlation between shoulder pain and the volume of residual carbon dioxide gas was due to this limitation.Second, in our study, none of the patients who underwent 1-port laparoscopy had a drainage tube because of the possibility of umbilical operative wound problems. The effect of the drain tube was not further analyzed in ruling out the potential factors influencing the amount of residual carbon dioxide gas. With this, our analysis of drainage tube use has some limitations. Although the drainage tube may be a main factor in decreasing the amount of residual carbon dioxide gas, other factors were suggested, including the additional port, total amount of insufflated carbon dioxide gas, operation time, and other factors that would be influenced by the amount of residual carbon dioxide gas.Third, because there were fewer enrolled patients in the 3-port group, the comparisons of clinical outcomes between the 2- and 3-port laparoscopy groups showed no significant differences. The study period of the retrospective cohort study was identified as the period during which 1 surgeon had performed laparoscopic adnexal surgeries in the hospital. For this reason, despite the small size of the study groups, bias resulting from the surgeon or medical treatment patterns can be excluded.Fourth, the enrolled patient study group was consecutive and was divided into 3 study groups according to the number of ports used. Propensity score matching was not performed.A retrospective cohort study was performed via a review of the medical records and radiological studies related to patients who underwent laparoscopic adnexal surgery between March 2005 and June 2018. The enrolled patients were divided into 3 study groups according to the number of ports used into the 1-port (198 patients), 2-port (114 patients), and 3-port (14 patients) groups.The total volume of postoperative residual carbon dioxide gas was significantly different between the 1- and 2-port groups and the 1- and 3-port groups. However, the difference between the 2- and 3-port groups was not significant. A drainage tube was used in all cases of 2-port and 3-port laparoscopy and played a major role in decreasing the volume of postoperative residual carbon dioxide gas. Clinical characteristics and operative outcomes were analyzed according to the use of a drainage tube. There were significant differences in the preoperative WBC, postoperative hospitalization duration, right residual carbon dioxide volume, left residual carbon dioxide volume, total residual carbon dioxide volume, and shoulder pain score between the groups with and without a drainage tube. Therefore, the use of a drainage tube played a role in decreasing the volume of residual carbon dioxide gas and lowering the pain scores without increasing the risk of postoperative infection.Although we found that the residual gas volume was less correlated with the shoulder pain score than with the operative wound pain score, we also found that the volume of residual carbon dioxide gas and the shoulder pain score were lower in patients with a drainage tube than in patients without a drainage tube. Although the drainage effect on shoulder pain has been controversial, a drainage tube can be safely used to decrease the residual carbon dioxide gas volume and pain scores without increasing the risk of postoperative infection.Conceptualization: Sang Wook Yi.Data collection: Sang Wook Yi.Methodology: Sang Wook Yi.Writing – original draft/review & editing: Sang Wook Yi.


Anxiety and pain levels of septoplasty patients may vary according to intraday operation time.To investigate the effects of septoplasty operation and intraday operation time on anxiety and postoperative pain.Ninety-eight voluntary patients filled out the hospital anxiety and depression scale to measure the anxiety level three weeks before, one hour before and one week after surgery. Forty-nine patients were operated at 8:00 am (morning group); other 49 were operated at 03:00 pm (afternoon group). We used a visual analogue scale to measure postoperative pain. Preoperative and postoperative scores were compared, as were the scores of the groups.p <  0.001), and one week after the operation [2 (1–6)] were significantly lower compared to the median scores three weeks before the operation [3 (1–6)] (p <  0.001). Hospital anxiety and depression scale scores one hour before the operation were significantly greater in the afternoon group [8 (7–10)], compared to the morning group [4 (2–6)] (p <  0.001). Postoperative first, sixth, twelfth and twenty-fourth-hour pain visual analogue scale scores were significantly higher in the afternoon group compared to the morning group (p <  0.001).Median hospital anxiety and depression scale scores one hour before the operation [6 (2–10)] were significantly higher compared to the median scores three weeks before the operation [3 (1–6)] (Septoplasty might have an increasing effect on short-term anxiety and postoperative pain. Performing this operation at a late hour in the day might further increase anxiety and pain. However, the latter has no long-term effect on anxiety. Septoplasty is one of the most frequently performed surgical procedures in an otolaryngology practice.Anxiety is an emotion characterized by feelings of tension and worried thoughts with an inexplicable cause. Anxiety and stress are among unpleasant feelings that may negatively affect the surgical operation and also the patient's recovery.Acute postoperative pain is defined as acute pain caused by the patient's pre-existing disease and/or surgical intervention he/she has undergone.Anxiety level might be affected by various factors like age, gender, failed surgical intervention, the size of the surgical procedure (minor/major), and operation time.This prospective, clinical study was conducted in line with the dictates of the World Medical Association Declaration of Helsinki and approved by the local ethical committee of Aksaray University (IRB Number: E-18-2419). Among the patients admitted to the Ear- Nose-Throat outpatient clinic, 98 voluntary adult patients mentally capable of filling out a scale/questionnaire were included in our study. The patients who had a known psychiatric disease, a history of antidepressant medication use and a previous history of facial surgery and facial trauma were excluded from the study. To determine the anxiety levels of the patients, we applied the Hospital Depression and Anxiety Scale (HADS) to the patients for preoperative evaluation, three weeks before, one hour before the operation, and one week after the operation. The HADS is an assessment scale that evaluates the patient for anxiety and depression. It includes a total of 14 questions. Odd numbers measure anxiety, and even numbers measure depression. The Hospital Anxiety and Depression Scale (HADS) was developed by Zigmond and Snaith in 1983.The difference between the HADS scores of the operation day (one hour before the operation) and the scores three weeks before the operation (difHADS) were calculated to determine the change in the HADS scores caused by the operation in the early period.The patients were instructed to use Visual Analog Scale  one hour before the operation and in the postoperative first, sixth, twelfth and twenty-fourth hours to measure the pain levels, and the VAS scores of all patients were recorded. The VAS is an individual pain assessment method, and it is used to measure pain directly by the patient.No patient received a sedative or analgesic before the operation. All patients underwent surgery under general anesthesia with endotracheal intubation. Forty- nine patients underwent septoplasty at 8.00 am (morning group) and 49 underwent surgery at 03.00 pm (afternoon group). The preoperative fasting time of all patients was equal (7–8 h). The average operation time was 20–30 min. No complication was seen during or after the operations. In postoperative pain treatment, all patients received paracetamol (10 mg/kg) 4 times a day as the standard procedure, and we did not use an additional analgesic. All patients stayed in the hospital for twenty-four hours after the operation for short-term follow-up. The overall median HADS scores of the operation day were compared to the overall median HADS scores three weeks before and one week after the operation. To investigate the effects of the operation time on the anxiety level of the patients, the HADS scores three weeks before, one hour before and one week after surgery were compared between the morning group and the afternoon group. Moreover, difHADS values were compared between the morning group and afternoon group. In addition, we investigated the correlation between postoperative sixth-hour pain VAS scores and HADS scores one hour before surgery.p <  0.05). To compare the overall HADS scores of the operation day (one hour before the operation) and the overall scores three weeks before the operation, Wilcoxon signed-rank test was used. To compare the HADS scores three weeks before, one hour before and one week after surgery, and to compare the difHADS between the morning group and the afternoon group, Mann-Whitney U test was used. To compare the pain VAS scores of the groups, Mann-Whitney U test was used as well. To investigate the correlation between the postoperative sixth-hour pain VAS scores and HADS scores one hour before surgery, the Spearman correlation test was used. All statistical analysis was performed using SPSS 16 software for Windows . A p-value under 0.05 was considered statistically significant.Results are presented as median (min‒max). The abnormal distribution of data was confirmed using the Kolmogorov-Smirnov normality test  underwent septoplasty at 8.00 a.m. (the morning group), and 49  underwent septoplasty at 03.00 pm (the afternoon group). The groups were age and gender- matched  .Table 1Dp <  0.001). On the other hand, the median HADS scores one week after the operation [2 (1–6)] were significantly lower compared to the median scores three weeks before the operation [3 (1–6)] (p <  0.001). Thus, we found that septoplasty operation had a significant short-term increasing effect on the anxiety levels of the patients regardless of the operation time, but the anxiety levels of the patients significantly decreased one week after surgery ] were significantly higher compared to the median scores three weeks before the operation [3 (1–6)] ( surgery .Table 2Cp =  0.767) and one week after the operation (p =  0.215) did not significantly differ between the groups. However, the HADS scores one hour before the operation were significantly greater in the afternoon group [8 (7–10)] compared to the morning group [4 (2–6)] (p <  0.001). Additionally, we found a significantly higher median difHADS in the afternoon group [5 (3–9)], compared to the morning group [0 (0–5)] (p <  0.001). Thus, we found that the late operation time had significantly more increasing effect on the anxiety levels of septoplasty patients (The HADS scores of the morning group and afternoon group are presented in patients .Table 3Cp < 0.001) (The pain VAS scores of the groups were shown in < 0.001) . Thus, wp < 0.001), positively, and strongly (rho = 0.78) correlated with the HADS scores one hour before the operation. Thus, we found that preoperative anxiety had a significant increasing effect on the pain levels of the patients undergoing septoplasty.In addition, postoperative sixth-hour pain VAS scores were significantly , positively, and strongly (rho = 0.78) correlated with the HADS scores one hour before surgery. Thus, we determined that preoperative anxiety had a significant increasing effect on the pain levels of the patients undergoing septoplasty.Many authors investigating preoperative anxiety levels concluded that patients with high levels of anxiety had more postoperative pain and used more analgesics.Janis claimed that a lower preoperative anxiety level was associated with better postoperative recovery while a higher preoperative anxiety level was associated with poorer postoperative recovery.The main limitation of our study is the relatively small study population leading to the lack of generalization. In addition, administration of the scales more than once in a week- interval would provide more accurate results. However, our results suggest that minor surgical interventions should not be shifted to too later hours, to avoid complications regarding increased anxiety and pain. Furthermore, in addition to analgesics, anxiety reduction strategies should be implemented to decrease postoperative pain in the patients undergoing septoplasty.The results of this study suggest that the septoplasty operation, which is described as a minor surgery, might have an increasing effect on short-term anxiety and postoperative pain, and performing this operation at a late hour might further increase anxiety and pain. However, it has no effect on anxiety in the later period. Anxiety reduction strategies should be implemented to decrease postoperative pain in the patients undergoing septoplasty.The authors declare no conflicts of interest.


Aim: Through this study, we aim to investigate whether biomarkers like the neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), and systemic immune-inflammatory index (SII) might predict the postoperative first 24 hours analgesic requirement and pain scores of patients undergoing laparoscopic cholecystectomy. Material & Method: After receiving the local ethical board approval, records of 67 patients, aged between 18 and 75 years, with ASA classifications I-III who underwent elective laparoscopic cholecystectomy were retrospectively evaluated to record postoperative analgesic requirements and numerical pain scale (NRS) scores. NLR, PLR, and SII scores were calculated from preoperative hemograms and compared with analgesic requirements and NRS scores.Results: The data of 67 patients were evaluated. There was no correlation between postoperative tramadol use and NRS scores, PLR, or SII values (p>0.05). NRS scores and the cumulative 24-hour postoperative tramadol use were correlated (p=0.0001), as it was observed that patients with high NRS scores used higher amounts of tramadol. Additionally, a poor statistically significant correlation was found between PDW (Platelet distribution width) value and tramadol dose (AUC = 0.611).Conclusion: No significant association between NLR, PLR, SII, pain scores, and tramadol use was detected.  The first laparoscopic cholecystectomy was performed in France in 1987, and it quickly became an alternative to open cholecystectomy throughout the world. It is a safe and efficient treatment for symptomatic gallstones .Postoperative pain occurs as an inflammatory reaction to surgical trauma. Incisions, dissection, retraction, and other surgical interventions lead to a local inflammatory mediator response, leading to an increase in nociceptor sensitivity and hyperalgesia, resulting in a sense of postoperative pain . NumerouNeutrophil/Lymphocyte Ratio (NLR) is a simple and inexpensive inflammatory response marker that has become increasingly popular in recent years -6. Also Our goal in this study is to determine whether there is a correlation between hemogram parameters and parameters obtained from hemograms, pain scores, and analgesic requirements in the postoperative 24-hour period in patients who have undergone LC surgery, and whether these have predictive value for pain conditions.ClinicalTrials.gov (NCT05558553) following approval by the local ethics committee (SUKAEK) on 29 June 2022 with decision number 2022/4/11.This retrospective study was registered on The records of patients aged 18 to 75 who underwent elective LC surgery between January 1, 2022, and August 31, 2022, and had ASA scores of I-III were evaluated using the hospital automation system (Fonet v4.22.10.1) and patient files. The study excluded individuals with hematological disease, immunosuppressive therapy, inflammatory disease, gastrointestinal tumor, rheumatic disease, uncontrolled diabetes, and chronic organ failure, as well as those who were corticosteroid and opioid users, obese, and who had open surgery. Those who had recently experienced cholecystitis or pancreatitis were also excluded. Age, gender, comorbidities, duration of surgery, presence of surgical complications, and hemodynamic and respiratory problems were extracted from the patient's medical records. The routinely used postoperative patient visit forms were used to collect the presence of postoperative nausea-vomiting, itching, NRS scores, opioid consumption, and further analgesic demands.Eleven parameters were recorded from the patients' preoperative complete blood count (Sysmex XN-3000). WBC (leukocyte count), RBC (erythrocyte count), PLT (platelet count), NEU (neutrophil count), LYM (lymphocyte count), MONO (monocyte count), EOS (eosinophil count), BASO (basophil count), MPV (mean platelet volume), PCT (percentage of thrombocytes) and PDW (platelet distribution width) were recorded. NLR (neutrophil to lymphocyte ratio) was calculated as absolute neutrophil count/lymphocyte count, PLR (platelet to lymphocyte ratio) as absolute platelet count/lymphocyte count, ELR (eosinophil to lymphocyte ratio) as absolute eosinophil count/lymphocyte count, and SII (systemic immune-inflammation index) as platelet count x neutrophil count/lymphocyte count. The patients' preoperative NLR, PLR, and SII scores at 24 hours were compared to their postoperative analgesic requirements and numerical pain scale (NRS) scores.The standard protocol for general anesthesia and analgesia was administered as follows. After evaluation and preparation for anesthesia before surgery, patients were transferred to the operating room. Endotracheal intubation was performed after anesthesia was induced using 2 mg/kg propofol, 2 mcg/kg fentanyl, and 0.6 mg/kg rocuronium in the operating room. Anesthesia was maintained with 50%/50% oxygen-air mixture, sevoflurane or desflurane at the appropriate minimum alveolar concentration (MAC), and remifentanil administered intravenously at 0.1-0.5 mcg/kg/min (iv). In accordance with our clinic's standard analgesia procedure, 1 g of intravenous paracetamol, 50 mg of intravenous tramadol, and 20 mg of intravenous tenoxicam were administered during the final 30 minutes of surgery. The patients were extubated after adequate reversal of muscle relaxant. Patients are administered 1 gr iv paracetamol every six hours, 20 mg iv tenoxicam every 12 hours, and tramadol iv patient-controlled analgesia (PCA) device as part of our institute's postoperative analgesic protocol. PCA included 100 ml of normal saline containing 350 mg of tramadol. PCA was set at 20 mg boluses (to be used when NRS ≥4) with a 20-minute lockout time, without basal infusion, and for a maximum dosage of 100 mg per four hours. If, despite, the aforementioned planned analgesia regime and PCA, the patient's NRS was four or above for more than two hours, then 0.05 mg/kg of intravenous morphine was used as rescue analgesia. Patients' 24th postoperative hour NRS scores at rest and during movement, the amount of analgesic administered, the need for additional analgesics, and the occurrence of nausea-vomiting were frequently monitored and documented on the postoperative patient evaluation form.Statistical analysisStatistical analysis was performed using SPSS Inc. Released 2009. PASW Statistics for Windows, Version 18.0. Chicago: SPSS Inc. Data are reported as mean, median, standard deviation, and percentage, where appropriate. Comparison of means between groups was compared using the t-test. Chi-square tests were used to compare categorical variables. Correlations were evaluated with the Receiver Operating Characteristics (ROC) curve. AUC (Area Under the Curve) values greater than 0.60 and p < 0.05 were accepted as having statistical significance.One hundred and fifty-four patients underwent LC during the study time. Of these, 67  were included in the study. The flow diagram for patient inclusion is shown in Figure The average age of patients was 50±13 years. When preoperative hemogram parameters, NRS scores at rest and during movement, and 24-hour tramadol consumption were compared, a statistical relationship was found between pain scores and tramadol use (p=0.0001). There was no relationship between patients' age, surgical time, hemogram parameters, and 24-hour tramadol use (p>0.05)  of tramadol. The two groups were similar with regards to age, gender, ASA classification, length of surgery, NLR, PLR, SII, NRSH, NRSI, WBC, RBC, PLT, NEU, LYM, MONO, EOS, BASO, MPV, PCT, and PDW (p>0.05) . There was only a statistically significant weak correlation between PDW and postoperative 24-hour tramadol consumption (AUC > 0.6) .Postoperative pain is an acute status of discomfort that commences with surgical trauma and diminishes as the tissue heals . Acute pThe pathophysiological pain classification system identifies nociceptive and neuropathic pathways as mechanisms of pain formation. Nociceptive pain is caused by damage to tissues such as internal organs, muscles, and/or bone, and it is classified into two types: somatic pain and visceral pain. Somatic pain develops as a result of injuries to the skin and musculoskeletal system. Somatic pain is further classified as superficial and deep somatic. For example, pain caused by a minor incision on the skin's surface causes superficial somatic pain, whereas hip fracture leads to deep somatic pain. Visceral pain, also known as referred pain, is discomfort that originates in the internal organs and is difficult to pinpoint . Numerouth-hour pain scores and NLR were correlated. The outcomes of these investigations are primarily regarding somatic pain. In another study, a substantial association was discovered between propofol injection pain and NLR, PLR, and SII, and these three measures were deemed predictive of propofol injection pain [Several studies, including those regarding postoperative pain, have shown a correlation between various pathologies with hemogram parameters and indexes. In a study involving 140 patients who had orthognathic surgery, Turgut et al.  reportedion pain .Another investigation on LC patients also revealed a link between NLR and surgical pain. In their study involving 60 patients who had LC, Daoudia et al.  assessedIn a study by Yiğit et al. , MPV andIn addition to their uses in predicting postoperative pain, it has been reported that hematological parameters like NLR, PLR, and lymphocyte-monocyte ratio (LMR) obtained from a hemogram are simple tests that can be used as reference indicators in the follow-up of rheumatological diseases to determine the systemic inflammatory . It has We believe that our findings can be explained by the fact that both visceral and somatic pain is prominent in patients undergoing LC. In addition to parameters such as NLR, PLR, and SII, that were evaluated in this study and which are especially useful in predicting inflammatory conditions, indices such as fibrinogen-albumin ratio, c-reactive protein (CRP) albumin ratio, albumin-fibrinogen ratio, erythrocyte sedimentation ratio are further biomarkers ,23 that Our study's retrospective design is one of its limitations. Propensity score matching could have remedied this issue; however, the number of patients was insufficient. We were only able to include 67 patients as we are unable to offer a PCA device to every patient undergoing LC in our institute. Markers like NLR, PLR, and SII are directly associated with chronic inflammation and can be influenced by a variety of factors such as obesity, dietary habits, smoking, acute infection, etc. To investigate the relationship between logistic regression analysis and independent variables, a prospective study can be done in homogenized groups, or more patients can be included in the study.In conclusion, parameters such as NLR, PLR, and SII, which are primarily used to predict the inflammatory response, are also used as simple, inexpensive, and easily accessible markers used to predict clinical course in various clinical scenarios. However, these factors were ineffective in predicting postoperative pain levels and tramadol use following LC. Randomized, controlled clinical trials are required to determine the efficacy of NLR, PLR, SII, and these biomarkers in predicting postoperative pain, particularly in laparoscopic procedures.


Intravenous paracetamol added to morphine reduces postoperative morphine consumption in (near)term neonates. However, there are only sparse data on intravenous paracetamol as multimodal strategy in extremely low birth weight (ELBW) neonates.This study aims to assess the effects of rescue intravenous paracetamol on postoperative pain management (≤48 h postoperatively) in relation to both analgesic efficacy  and safety (hypotension and bradycardia). This rescue practice was part of a standardized pain management approach in a single neonatal intensive care unit (NICU).A single-center retrospective observational study included 20 ELBW neonates, who underwent major abdominal surgery. The primary endpoints of the postoperative study period were pain intensity, over-sedation, time to first rescue analgesic dose, and the effect of paracetamol on opiate consumption. Secondary endpoints were safety parameters . And as tertiary endpoints, the determinants of long-term outcome were evaluated .p < 0.05). All long-term outcome findings were similar between both groups.All neonates received continuous opioids (sufentanil or morphine) and 13/20 also intravenous paracetamol as rescue pain medication during a 48-h postoperative period. Although opioid consumption was equal in the non-paracetamol and the paracetamol group over 48 h, the non-paracetamol group was characterized by oversedation (COMFORTneo < 9), a higher incidence of severe hypotension, and younger postnatal age (Our study focused on postoperative pain management in ELBW neonates, and showed that intravenous paracetamol seems to be safe. Prospective validation of dosage regimens of analgesic drugs is needed to achieve efficacy goals. In 2016, a multidisciplinary ESPNIC  position statement was published guiding professionals in assessing and re-evaluating treatment interventions for pain, distress, inadequate sedation, withdrawal syndrome, and delirium in the pediatric populations for various pain profiles across ages –5. HowevUnfortunately, the treatment of ELBW neonates is still difficult at present, and setting the key endpoints in neonatal analgesic clinical trials is necessary , 12. FirThis is, even more, the case in the specific setting of pain management in ELBW for necrotizing enterocolitis or abdominal surgery, as recently observed by ten Barge et al. . In theiConsequently, this study aimed to evaluate the unit protocol for postoperative pain management (≤48 h) to achieve postoperative analgesic efficacy goals  after major abdominal surgery in ELBW infants. This standardized local approach included the use of single-dose paracetamol as a rescue drug. We hereby documented drug utilization, effective drug dosing  as well as safety parameters  related to the use of analgesics and sedatives in ELBW neonates.The retrospective single unit study included ELBW neonates admitted to the Level III NICU of General University Hospital, 1st Faculty of Medicine of the Charles University in Prague, Czech Republic, who underwent acute major abdominal surgery between January 2014 and December 2019. An institutional review board (IRB) approval for publication of the study was obtained (No. 117 248/21 S-IV). The use of anonymous data for scientific purposes is part of general informed consent, which parents signed during admission to the hospital.Inclusion criteria were birth weight (BW) <1,000 g and gestational age (GA) ≤28 weeks; abdominal surgery  by postmenstrual age (PMA) ≤36 weeks.Exclusion criteria were the refusal of an informed consent form. One of the operated patients was excluded for infaust prognosis  and decision of care termination at the time of surgery. Furthermore, we did not enroll the same patients undergoing the second planned operation (stoma closure), because the planned operations and the first days of postoperative care took place in another center.n = 13; and a non-paracetamol (non-P) group, n = 7. In all cases, a treatment period until 48 h post-surgery was assessed.Enrolled neonates were stratified into two groups according to paracetamol administration as rescue analgesic therapy: a paracetamol (P) group, Demographic characteristics were collected: weeks of gestational age (GA), postmenstrual age (PMA) at surgery, birth weight (BW) and the actual body weight at surgery (g), gender , Apgar score, and diagnosis (indication for surgery).th percentile-a short episode without treatment or an episode treated with catecholamines) were the secondary endpoints of the study.The primary endpoints parameters were pain intensity, over-sedation, time to first rescue analgesic dose, and the effect of paracetamol on opiate consumption. Safety parameters  and breastfeeding on hospital discharge; and long-term neurodevelopmental outcomes evaluated by Bayley Scales of Infant Development-BSID-II-mental (MDI) and psychomotor (PDI) developmental index-standardized in infants .As long-term outcome parameters (tertiary endpoints) were evaluated mechanical ventilation duration, length of hospital stay, grade of intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL), stage of chronic lung disease (CLD); postnatal growth restriction . The obvious pain score is a locally adapted and internally validated score that simplifies a subjective evaluation system such as the Numeric Rating Scale (NRS) for moderate and severe pain (NRS ≥ 4). Obvious pain assessment is a part of the nurses' daily documentation evaluated at least once every 3–6 h. COMFORTneo is a validated pain score even for very premature neonates, consisting of 6 behavioral items  . In our Analgesic drug dosages were based on standardized international guidelines , 18–20. The indication for the rescue paracetamol administration was either one event with a COMFORTneo > 14 or one observation of obvious pain, or both.Paracetamol  was administrated intravenously (dose 7.5 mg/kg as a single dose or every 6–8 h over 15 min). The loading dose of paracetamol was not administered at that period.Morphine given an initial bolus (10–40 μg/kg/ over 10 min) followed by a continuous intravenous infusion .Sufentanil , an initial bolus of 0.2 μg/kg administered for 10 min intravenously followed by a continuous infusion of 0.05-0.2 μg/kg/h. Sufentanil average daily dose was converted to morphine equivalents (IV sufentanil 0.1 mg = IV morphine 100 mg) ( 100 mg) , 22.Ketamine , given in a single dose (2–3 mg/kg).Propofol , given in a single dose (2 mg/kg).Basic features were summarized by descriptive statistics such as median, interquartile range (IQR), or range of variables. Mann–Whitney (U-test) or Fisher's exact test was used to comparing patients exposed to paracetamol (P-group) to those without paracetamol (non-P group) exposure. The results are reported in the form of the median (IQR).Of the 1,277 NICU admissions during the study period 2014-2019 about 417 patients were ELBW neonates . Forty eight suffered from NEC , and 8 neonates were diagnosed with SIP (pneumoperitoneum on X-ray). Surgical treatment was indicated in 17 patients with NEC, 4 patients with SIP, and 1 patient with volvulus.+1 - 25+2). A statistically significant difference between the P and non-P groups was found in median PMA at the time of surgery, in the P group at 28 weeks and 2 days (27+0 - 30+0) vs. non-P group at 26 weeks and 3 days (26+2−26+6), thus 29 vs. 8 days of postnatal age, respectively, (p = 0.034). The most frequent surgical diagnosis was necrotizing enterocolitis (NEC) in 15 cases, spontaneous intestinal perforation (SIP) was diagnosed in 4 cases, and bowel obstruction in 1 patient, none of the included patients died during the study period.The characteristics of the studied population are shown in All enrolled patients were scored with a COMFORTneo scale. In addition, the nurses reported “obvious pain,” when the discomfort was noted. The nurses performed approximately five COMFORTneo assessments per day on each patient. During the 48-h follow-up period, 57% of the measured COMFORTneo scores were in the target range –14, whicp = 0.015, U-test) . Intravenous paracetamol RD was indicated if COMFORTneo exceeded 14 (n = 1), when obvious pain was observed (n = 6), or both (n = 4). In 2 patients, paracetamol was added immediately after surgery without documented increased pain score. Accordingly, paracetamol RD was administrated in 10/13 cases although the median (IQR) COMFORTneo score was 12 (9-13.3), i.e. within the target.The non-P group had lower scores than the P group, significantly during the first 24 h after surgery ( U-test) . The scoThe reassessment of the COMFORTneo was performed 5 (4–6) h after the RD because the patients were considered as comfortable and no obvious pain was reported. And the reassessment median score was insignificantly worse 13.9 (11-15) than the previous.During the 48-h treatment period, all patients received continuous opioids, 13 patients (65%) received sufentanil, 12 patients (60%) morphine, 5 patients (25%) both sufentanil and morphine consecutively). Sixteen patients (80%) required an additional bolus analgesic drug to achieve sufficient pain control. The time to the first rescue dose was the median (IQR) 11.5 (3.5–24) h. Of these, 13 (81.3%) received paracetamol, 6 patients (37.5%) had ketamine, 4 patients (25%) received an additional opioid bolus and 1 patient (6.3%) propofol. The average analgesic daily dosage is shown in p = 0.012, Fisher's test) (Safety parameters such as bradycardia (<80/min) event were observed in 2 patients in the P group (10%), while no severe bradycardia was documented in the non-P group patients. In contrast, events of serious hypotension (treated with catecholamines) were more commonly documented in the non-P group ('s test) .The tertiary endpoints are shown also in The main goal of this retrospective study was to generate additional data on the efficacy of paracetamol (effects to reduce postoperative pain) and its safety in ELBW neonates following major abdominal surgery. In this specific setting, and taking the limitations of the small cohort into account, paracetamol rescue medication was associated with less oversedation, suggesting safe postoperative analgesia in this population. Other quality care indicators, such as length of invasive mechanical ventilation or length of hospital stay and long-term outcome according to Bayley II developmental indexes, IVH, PLV, and CLD were similar in both the paracetamol (P) and non-paracetamol (non-P) groups of patients. Additionally, a detailed multimodal analysis focused on identifying deficiencies in pre-existing local postoperative pain management in the neonatal intensive care unit.According to COMFORTneo, adequate pain control was only partially achieved in patients treated with paracetamol. On the other hand, the non-paracetamol group showed oversedation together along with more severe hypotension. Interestingly, the non-P group was significantly younger at the time of the surgery  and more vulnerable as speculated. Based on a local unit protocol, the rescue dose (RD) of intravenous paracetamol was administered to eleven neonates while in two patients, RD was added to analgesic drugs “routinely.” The median (IQR) COMFORTneo before the RD of paracetamol was 12 (9–13.3) within the target range but the decision to give the RD of paracetamol was based on the current situation when the neonate was considered as “uncomfortable” based on the standardized treatment protocol. The median (IQR) COMFORTneo after the RD was 13.9 –15, but It seems the use of paracetamol in the “rescue” regimen was not significant in its effects to reduce the dose of opiates or the number of other analgesic boluses administered during the study period. The possible explanations may be (1) lack of consistency of caregivers in reassessing pain scores after interventions, as the daily number of assessments was the same between groups; (2) age-related differences in opiate pharmacokinetics; and (3) possible differences in interindividual disease characteristics and developmental changes in pain perception . KrekelsOpiates have been widely used analgesic agents in neonatal intensive care units in the past few decades despite negative short-term side effects and possible long-term neurobehavioral consequences for premature individuals –32. In cThis study was performed to evaluate a standardized approach to postoperative pain (≤48 h) to achieve postoperative analgesic efficacy and safety objectives in ELBW neonates and meant as a baseline study for internal prospective validation of postoperative analgesia conducted in this population. The limitations of this study were, for example, the design of a retrospective observational study, the small sample size, and the initial phase of scoring implementation without an adequate reliability score among the caregivers' evidence. Another limiting factor of a designed postoperative follow-up period could be the amount of medication taken before and during surgery and the possible tolerance to opiates, especially in postnatally older patients. However, the median days of continuous opiate use preoperatively and their dosing did not statistically differ between the two study groups.Therefore, implementing appropriate age-related dosing of opioids co-administered with intravenous paracetamol, including a loading dose, and setting up an educational program to achieve the best consistency and inter-rater reliability of healthcare professionals in pain assessment methods are the main goals of the prospective study. In addition, supporting parental contributions should be part of daily clinical practice. These interventions are the future direction of our project.The introduction of intravenous paracetamol as a rescue medication in ELBW neonates after abdominal surgery was safe analgesia, although it did not reduce opiate consumption in the rescue regimen. Prospective validation is needed to optimize postoperative analgesia according to analgesic efficacy and safety goals in this population.The original contributions presented in the study are included in the article/https://www.vfn.cz › odbornici › eticka-komise › informace). Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.The studies involving human participants were reviewed and approved by Ethics Committee of General University Hospital in Prague (available at HC contributed to conceptualization, data curation, investigation, methodology, and writing—original draft. LB contributed to formal analysis and visualization. BZ contributed to investigation and resources. KA contributed to supervision and writing—original draft. PP contributed to conceptualization, methodology, project administration, supervision, and writing—original draft. All authors contributed to the article and approved the submitted version.This work was supported by the Ministry of Health of the Czech Republic [RVO VFN 64165]; and Charles University [UNCE 204064]. PP was supported by an unrestricted research grant of the Intensive Care of the Erasmus MC-Sophia Children's Hospital and Progress Q25.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. 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Previous findings indicated that breast cancer patients often have dysfunction in empathy and other cognitive functions during or after chemotherapy. However, the manifestations and possible neuro-electrophysiological mechanisms of pain empathy impairment in breast cancer patients after chemotherapy were still unknown.The current study aimed to investigate the potential correlations between pain empathy impairment and event-related potentials (ERP) in breast cancer patients undergoing chemotherapy.Twenty-two breast cancer patients were evaluated on a neuropsychological test and pain empathy paradigm before and after chemotherapy, containing the Chinese version of the Interpersonal Reactivity Index (IRI-C), while recording ERP data.t = 3.039, p < 0.01; t = −2.324, p < 0.05, respectively). Meanwhile, the accuracy rates were lower than those before chemotherapy for both pain and laterality tasks on the pain empathy paradigm . However, the response time was no significant differences before and after chemotherapy . Further, the amplitude of the N1 component was significantly increased , and the amplitude of the P2 component was significantly decreased  in the subsequent ERP study. A linear mixed effect model was used to analyze the correlation, the average amplitude of N1 and P2 were positively correlated with the accuracy rates in laterality tasks .The empathic concern scores were lower and personal distress scores were higher on IRI-C task compared with those before chemotherapy (The results indicated that pain empathy impairment was performed in chemotherapeutic breast cancer patients, which was possibly correlated to the changes of N1 and P2 components in ERP. These findings provide neuro-electrophysiological information about chemo-brain in breast cancer patients. Breast cancer was the most frequent malignancy in women, occupying 30% of all new cancer cases diagnosed in women from the published data of the American Cancer Society . The incCancer patients tended to have more emotional problems in terms of pain, such as fear and sadness in comparison with healthy individuals . EmpathyEvent-related potential is a highly sensitive and non-invasive technique, which is commonly used in the area of psychology and cognitive neuroscience, with an accuracy of up to milliseconds, and can permit the evaluation of pain empathy . Breast Breast cancer patients would feel inferior and depressed due to the incomplete body after radical mastectomy, meanwhile, chemotherapy could also reduce their concern for surrounding things, resulting in emotional regulation and empathy impairment, which would even persist for several years . HoweverIn this study, 22 breast cancer patients who accept chemotherapy were enrolled and cognitive test, pain empathy paradigm, and ERP studies were completed before and after chemotherapy, trying to confirm the specific performance on pain empathy, to further clarify the correlations between pain empathy impairment and ERP in breast cancer patients undergoing chemotherapy.Twenty-two patients with breast cancer were volunteered from 2017 to 2019 in the Department of Oncology, the Affiliated Second Hospital of Anhui Medical University. The Research Ethics Committee of the Affiliated Second Hospital of Anhui Medical University, China, authorized the study (protocol 20131028). The informed consent were obtained for all subjects. All participants had normal vision and could cooperate well with the inspection. Inclusion criteria: (1) Diagnosed with breast cancer and completing at least six cycles of chemotherapy; (2) Anthracycline-based chemotherapy regimens; (3) No language or other communication barriers; (4) normal daily activities could be acquired, KPS scores ≥80. Exclusion criteria: (1) history of psychotropic medications; (2) dementia, anxiety, and/or other psychiatric illnesses; (3) a history of radiotherapy and endocrine therapy; (4) brain metastases; (5) Abuse of alcohol or illicit drugs.Participants took part in the following tasks before and after chemotherapy. A mini mental state examination (MMSE) which included orientation, memory, attention, computation, recall, and language served as a screening tool for overall cognition, for which the total possible score was 30 points . Digit sAdd up to 120 pictures were applied to the pain empathy paradigm, depicting human hands and feet under painful or neutral stimulation, but without facial expressions. All painful stimulation events could happen at any time in daily life, such as catching the left (or right) hand in closing doors and windows, cutting the left (or right) fingers on a kitchen knife, and other daily mishaps.The pain empathy paradigm consisted of pain and laterality tasks. The participants were required to determine whether the people in the photo felt pain and hit the corresponding computer key  in the pain task. Additionally, participants were required to judge the left and right hands or feet being shown in the painful stimulation picture and to hit the corresponding computer key  in the laterality task. Each task included 60 pained and 60 neutral photos. Each trial required participants to make judgments as quickly and accurately as possible over a random period of time between 1500 and 1700 ms. The participants were trained by practicing the tasks for 20 pictures before the experiment proper began under the direction of a laboratory technician. Meanwhile, the ERP data was recorded on the pain empathy paradigm task .The ERP of the subjects was collected on a Neuroscan recording system  through the 64 electrode cap in this experiment. The reference electrode was positioned at the left mastoid of the subjects, and the grounding lead was attached to the central point of the forehead, recording the vertical and horizontal electrooculograms. The impedances of the skin and electrode needed to be adjusted to less than 10 kΩ, and the sampling rate was 1000 Hz, filtering broadband was 0.05–100 Hz. The digital Filtering channel was 32 Hz/24 (dB/Octave), and the length of analysis time was the appearance of stimulus from the first 200 ms to the later 1000 ms, and removing artifact proceeded on amplitudes exceeding ±100 μV. The mean value of electrode signals at the bilateral mastoid process was regarded as a reference, all electrooculograms were rectified by correlation regression analysis. Referring to previous research and the grand-average potential of each task condition, N1 (50–150 ms) and P2 (150–200 ms) were analyzed for ERP data in this study, and two frontal  and central electrodes (cz) were chosen for statistical evaluation of the ERPs.1; Chicago, IL, United States) was administered for statistical analysis. Student’s t-tests were performed for baseline information. Paired-sample t-tests were performed for cognitive testing pre- and post-chemotherapy. The reaction time and accuracy rate for pain and laterality tasks were committed to repeated-measures ANOVAs with time, task, and stimuli as within-subject factors. Similarly, the repeated-measures ANOVAs was also performed for the N1 and P2 component of ERP, and four within-subject factors refer to time point, task, and stimuli as well as electrodes (fz vs. fcz vs. cz). All the results were corrected according to the Greenhouse-Geisser method. A linear mixed effect model was conducted to analyze the correlation via MLwiN2.30 software. SAS/STAT software (version 9.4) was applied to draw forest plots. Statistical significance was described as P < 0.05.The SPSS software (version 22.0Years of education (7.1 ± 3.0) and KPS (90.5 ± 5.8) are shown for these participants.P < 0.05). The MMSE , VFT  and DSF  showed no significant difference before and after chemotherapy.p < 0.01) and higher on personal distress  as compared to those before chemotherapy , and had a significant difference (p > 0.05) and perspective taking  had no significant differences before and after chemotherapy.The IRI-C scores were lower on empathic concern , with a statistical difference. The main effect of the task was significant , and the accuracy of the laterality tasks was higher than that of the pain task . The main effect of stimuli was significant , and the accuracy rate of pain stimuli was lower than that of neutral stimuli , and there was no significant interaction in time (before vs. after chemotherapy) × stimuli  × task  . However, the response time was no significant difference before and after chemotherapy , the main effect of the task was significant , while there was no significant interaction between time, task, and stimulus .As revealed in F = 38.091, P < 0.001). The interactive effect was found in time and stimuli . There were also interaction effects among time × stimulus × task , and the main effects of task, stimuli, and electrode were not significant in the results. As for the P2 component, the peak amplitude after chemotherapy was significantly smaller in comparison to these before chemotherapy, showing a statistically significant difference . The main effect of the stimuli was significant , which means that the pain picture stimulation induced greater amplitude, resulting in a pain effect. There was no interaction between stimulus, task, and electrode.As shown in r = 1.765, P < 0.05). The mean amplitude of N1 at the fcz, fz, and cz electrodes were correlated with the accuracy rates for painful picture stimulation in the pain task . The mean amplitude of N1 at the cz electrode was correlated with accuracy rates for neutral picture stimulation in the pain task . Similarly, the amplitude of P2 at the fz electrode was positively correlated with the accuracy rates for painful picture stimulation in laterality tasks   , 7.The present study examined changes in pain empathy in breast cancer patients before and after chemotherapy by using the IRI-C scale and pain empathy paradigm with a concurrent recording of ERP. The results indicated that: (1) Breast cancer patients after chemotherapy achieved significantly lower scores in DSB tests, lower empathic concern, and higher personal distress as compared to the baseline; (2) Breast cancer patients showed a lower accuracy rate after chemotherapy treatment and for painful pictures stimulation as compared to neutral images in both pain and laterality task; (3) The ERP study indicated that the amplitude of N1 component was significantly increased and the amplitude of P2 component was significantly decreased after chemotherapy as compared to before chemotherapy; (4) The positive correlations was confirmed between the average amplitude of N1, P2 and pain empathy through linear mixed effect model analysis.Empathy involves different components, of which cognitive and affective empathy are relatively independent parts . Among tThe lower accuracy rate was performed in both pain and laterality tasks on the pain empathy paradigm in this study. Possible reasons were as follows. The modification of brain structure and function appeared in breast cancer patients after chemotherapy, which might cause associated cognitive dysfunction . McDonalBreast cancer patients exhibited a lower accuracy rate in judging images of pain stimuli than neutral stimuli in this study, both before and after chemotherapy. This might be related to the fact that the identification, evaluation, and processing of painful stimuli were more complicated than neutral for individuals. The study found that more areas of the brain were activated in response to painful stimuli than in comparison to neutral stimuli . The corThe ERP component (N1) was associated with pain perception caused by gender discrimination . ParticiSome limitations need to be discussed in this study. First, this study was a small sample and single-center research. A larger sample size and longitudinal design should be promoted in the next study. Second, the specific brain area associated with pain empathy impairment after chemotherapy had not been approved, and further research could be combined with functional magnetic resonance imaging to remedy this deficiency.In a word, the present study provided direct evidence for pain empathy impairment in breast cancer patients after chemotherapy and preliminarily demonstrated the variation in ERP  components associated with pain empathy. The findings extend the scope of CRCI and furnish a theoretical basis for improving the quality of life in breast cancer patients following chemotherapy.The original contributions presented in this study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by the Research Ethics Committee of the Affiliated Second Hospital of Anhui Medical University, China, authorized the study (protocol 20131028). The informed consents were accomplished for all subjects. The patients/participants provided their written informed consent to participate in this study.WL performed the cognitive tests and wrote the manuscript. YL performed the data analysis and pain empathy paradigm. XD performed the data collection. GC performed the statistical analysis of the data and refined the English language. SBY and SY performed the literature review. LT performed the clinical data acquisition. HC designed the project. All authors contributed to manuscript editing.


Analgesic opioid (AO) misuse by patients ranges from 0% to 50%. General practitioners are the first prescribers of AO. Our objective was to validate the Prescription Opioid Misuse Index (POMI) in primary care. We conducted a psychometric study in patients with chronic pain who had been taking AOs for at least 3 months and were followed in general practice. Patients responded to the POMI at inclusion and after 2 weeks. The reference used was the DSM-V. Sixty-nine GPs included 160 patients , mean age 56.4 ± 15.2 years. The total POMI score was 1.50 ± 1.27, and 73/160 (45.6.0%) had a score ≥ 2 (misuse threshold). Internal validity was measured with the Kuder–Richardson coefficient, which was 0.44. Correlations between each item and the total score ranged from 0.06 to 0.35. Test–retest reliability was determined from 145 patients: Lin’s concordance coefficient was 0.57 . Correlation with the DSM-V (Spearman’s coefficient) was 0.52. The POMI does not have sufficient psychometric properties to be recommended as a tool to identify the misuse of AOs in primary care. This study clearly showed that there is a need to create a monitoring tool specific to primary care. Chronic pain is a major issue in terms of the impact on the individual’s quality of life  and on sIn 2015, nearly one in five French people 17.1%) underwent opioid treatment .1% under. AmericaThe difficulty establishing the prevalence of misuse results from the lack of standardization of studies and the lack of consensus in the use of assessment tools. Several tools are available internationally ,11. The In 2015, treatment was initiated by a GP in 59.1% of cases for weak opioids and 62.9% of cases for strong opioids and by a hospital doctor for 20.1% and 21% respectively . CurrentThe aim of the study was to validate the French version of the Prescription Opioid Misuse Index (POMI) in patients with chronic pain  in a general practice setting.To study the profile of patients who misuse opioid analgesicsTo compare the results of this study with those of a previous study of patients followed in a pain clinic We conducted a prospective, observational and multicenter psychometric study to cross-culturally validate an opioid analgesic misuse screening scale (POMI) in patients with chronic pain in primary care in France. The study was registered on Clinicaltrial.gov: NCT05431985.All GPs working in general practices in four areas of France  were personally invited by email to take part in the trial. GPs who had undergone specialized training in addiction treatment  were not included. GPs included patients regardless of the motive for consultation.Patients aged 18 years and overPatients with chronic pain  for at least 6 monthsPatients with a GP prescription for at least one opioid analgesic drug taken daily for at least the previous 3 monthsPatients registered with the French insurance systemDiscontinuation of opioid prescriptions on the test step day (no retest possible)Patients in the process of withdrawal (risk of cessation during the retest step)Patients unable to complete the questionnaire alonePatients monitored by a pain clinic or addiction centerPatients with ongoing cancerPatients who refused to participateThe Prescription Opioid Misuse Index (POMI) was developed in the United States to assess oxycodone misuse. This scale was validated in 137 subjects recruited from pain clinics, addiction treatment programs, jails, or private medical practice . The POMAlthough this scale was validated for oxycodone, the evaluation also applies to other opioids . Misuse does not differ between categories of opioids, and no differentiation between categories is proposed by other validated scales. We also chose this scale because of its reliable scoring and performance, which are two important criteria for the broad use of such a tool in primary care.Knisely et al.  found thGPs completed the DSM-V questionnaire . As otheGPs asked patients about their medical history; type of pain ; duration of pain ; pain severity at its “worst” and “average”, measured with a numeric rating scale (NRS) (no pain = 0 to unbearable pain = 10); treatment . They collected the type of analgesia used: analgesic opioids, non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol, nefopam, and antimigraine drugs. The average daily dosage and duration of treatment  were collected.GPs asked patients about sociodemographic data ; medical and family medical history; history of psychiatric disorders; and substance use and abuse.The translation of the POMI scale to French was conducted according to the recommended cross-cultural adaptation process : transl.GPs were recruited by general medicine academic departments or research networks and patients were recruited from 16 January 2017 to 3 March 2019. GPs then received a brief e-learning training course (8 min) on the problem of investigating and setting up the study.Each GP was asked to include three consecutive patients regardless of the reason for consultation if they fulfilled the inclusion criteria, without anticipating possible misuse, over a period of 24 months. Patients were given an information letter summarizing the goals of the study. GPs informed patients that the data would be anonymized and strictly confidential and that that their decision to take part in the study or not would not impact their treatment in any way.At inclusion (test phase), GPs performed a clinical examination and assessed items of the DSM-V diagnostic criteria. The patient replied to the POMI questionnaire without the help of the GP. Completion time was around 15 min.At the end of the consultation, the GP gave the patient the retest questionnaire, containing only the POMI scale and a pre-stamped envelope.The retest step was conducted within 2 to 4 weeks after the test step. Patients sent the POMI scale completed it at home, then took it back to the coordination center. If necessary, a reminder was sent 10 days after the theoretical return date.Sample size estimation was fixed according to the COSMIN recommendations . AccordiThe statistical analyses performed in this study were those usually performed in studies to validate scales . In addiContinuous variables are presented as means and standard deviations or medians and inter-quartiles. To compare patient characteristics according to DMS-V results (<4/≥4) and to compare patient characteristics from this study (primary care) and the pain-clinic study, Chi-squared and Fisher’s exact tests were used for categorical data and Student t-tests or Mann–Whitney tests were applied for continuous variables. Homoscedasticity was evaluated with the Fisher–Snedecor test. All statistical tests were performed for a two-tailed type I error at 5%.Then, analyses were completed by factorial analysis to compare the characteristics of the pain-clinic-study patients and the primary-care patients. More precisely, mixed data factorial analysis, combining categorical and continuous data, was conducted with the following variables: age, sex, employment, pain type, and treatment. These variables were chosen according to the univariate results, their clinical relevance, and their statistical distribution . Group (participants in the pain clinic study and participants in the primary-care study) was treated as an illustrative variable. Only individuals without missing data were included in the factorial analysis. This exploratory method was used to summarize the relationships between variables and to detect the underlying structure of the data, i.e., patterns of patients. A sensitivity analysis was conducted to study the impact of missing data on results comparing the samples with and without missing data for the main patient characteristics.We recruited 69 GPs, 68 of whom included at least one patient. They were 42.8 years old [min 29–max 65], lived mostly in urban areas (78.0%), and 34/68 (50.0%) were female.From January 2017 to March 2019, the GPs included 160 patients, 87/160 (54.4%) were female, and the mean age was 56.4 ± 15.2 years. Descriptive statistics are shown in n = 98), and 55.6% (n = 89) of patients had had pain for at least 5 years. The main types of opioid analgesia used were tramadol , followed by codeine , oxycodone , and morphine . The frequently used non-opioid analgesia was acetaminophen  and NSAID .Type of pain was mainly nociplastic . The rate of patients who responded positively to individual items was lowest for Items 7 and 8  and highest for Items 2 and 6 .The results for the data quality and acceptability of the POMI scale are shown in Test–retest reliability was determined in 140 patients. For the POMI total score, Lin’s concordance coefficient was 0.57 , with 1.50 ± 1.27 at the test step and 1.01 ± 1.16 at retest. When the POMI score was dichotomized by a cut-off of 2, Kappa’s Cohen concordance coefficient was 0.42, with 72.9% agreement.For the POMI score excluding Items 6 and 7, Lin’s concordance coefficient was 0.55 , with 1.03 ± 1.08 for the test step and 0.65 ± 0.96 for retest. When the POMI score was dichotomized by a cut-off of 2, Kappa’s Cohen concordance coefficient was 0.38, with 78.6% agreement.p < 0.001). When POMI and DSM-V were respectively categorized as <2, >2 and <4, 4, or 5, ≥6, 82/160 patients had a score of <2 and <4, and 28/160 had ≥2 and ≥4 as expected, whereas 50/160 patients had ≥2 and <4 or <2 and ≥4.The correlation between the POMI score and DSM-V was r = 0.52  127/160 (79.4%) and a moderate to severe addiction (≥4) 33/160 (20.6%), p = 0.001), more often single (p = 0.03), more often inactive, or in a situation of disability (p = 0.01). There was no difference in type of pain and treatment according to the addiction score.Some sociodemographic differences were found between these groups: patients with moderate or severe addiction were younger , less often in a relationship (92 (57.5%) vs. 103 (73.1%), p < 0.001). They more often had nociceptive pain (83 (51.9%) vs. 33 (21.4%), p < 0.001), higher pain intensity in the last 24 h , and they have been in pain for less time. Many of them took codeine (35 (21.91%) vs. 17 (11.0%), p < 0.01) and paracetamol (85 (53.1) vs. 59 (38.3), p < 0.001)  .For the factorial analysis, 21 out of 314 (6.7%) patients were removed because of missing data, and 293 were retained. Vector analysis identified that the variables were distributed differently in the samples of the two studies . The twoThis is the first validity study of a European-French version of the Prescription Opioid Misuse Index (POMI) in patients with chronic pain  followed in a primary-care setting. We found that the psychometric properties of the POMI were insufficient to be used in primary care. Internal consistency measured with the Kuder–Richardson coefficient in 160 patients was moderate (0.44); almost half of the sample (45.6%) showed misuse (score ≥ 2). The item–rest correlation for the total score ranged from 0.06 to 0.35. Test–retest reliability in 140 patients was moderate . The POMI score was moderately correlated (r = 0.52) with the DSM-V score, which was the reference.Our study sample was similar to the French population of opioid users described in 2019 by ANSM , althougp < 0.001) vs. r = 0.45, p < 0.001).To validate the psychometric quality of a test, a Cronbach alpha of 0.7 is expected ,19. The Classified according to DSM-V score, non-misusers were older and more often in a relationship, but there were no major differences in terms of pain (type or duration) or treatment (opioids or non-opioids). On the other hand, the profiles of the patients differed between the samples of the two studies. Patients recruited in primary-care centers were older, more often had nociceptive pain, had higher pain intensities in the last 24 h, and have been in pain for less time. They more often took codeine and paracetamol but less often gabapentin. These results suggest that it is the difference between samples that led to the weaker psychometric properties of the tool when used in primary care. A tool specific to this population should therefore be developed.Over the past 10 years, GP consultations have been enriched by the availability of a multitude of tools . Around Lack of time and training were also cited as barriers to using a screening tool . The POMThe recruitment of patients in a GP practice is sometimes complicated. Not all GPs included patients, and those who did were able to choose the patients they included. During the test phase, the questionnaires were completed by patients in front of a clinician, and during the retest step, the same version was completed at home by patients. The test–retest reliability may have been affected by social desirability bias . We usedGPs are the first prescribers of opioids. Misuse, which is a broader concept than addiction, can be assessed at two stages: before the first prescription to identify the risk of developing misuse and during treatment to identify misuse. A misuse identification tool adapted to primary care would facilitate GP awareness of the two stages, as well as the correct use of opioid analgesics. This study clearly showed that there is a need to create a monitoring tool specific to primary care, that ensures the safe prescription of opioid analgesics by standardized and quick, regular monitoring in agreement with national and international recommendations.