Evaluation of the effects of gradual increases in intra-abdominal pressure on blood pressure in a patient undergoing laparoscopic cholecystectomy.

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Mohamadreza Abedinzade, Negin Taghavi, Nafise Mohamadi Farsani This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4601648/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Backgrounds Gallbladder stones are a common health problem in developed countries, and the laparoscopic surgical method is widely used for treatment. It is important to identify surgical techniques that can reduce complications during and after surgery. Methods This study included 100 patients, with 50 in the intervention group who underwent surgery with stepwise increased intra-abdominal pressure, and 50 in the control group who had surgery with 15 mmHg pressure. Demographic information was recorded, and hemodynamic changes during surgery and postoperative complications were documented. Data was compared using independent t-tests, ANOVA, and Chi-square tests. Results The results of our study showed that the intervention group had significantly more stable mean heart rate and blood pressure (systolic, diastolic, and mean arterial pressure) during surgery compared to the control group. The intervention group also had significantly lower frequency of nausea, mean pain, and administration of the analgesic Pethidine during recovery. However, there were no significant differences between the two study groups in mean arterial oxygen saturation during surgery, duration of hospital stay in recovery, frequency of vomiting, and headache. Conclusion Based on our findings, it is recommended to increase intra-abdominal pressure using the stepwise method employed in our study for all patients undergoing cholecystectomy. This can help achieve hemodynamic stability during surgery, reduce pain in patients, and improve the overall quality of treatment. Intra-abdominal pressure laparoscopic cholecystectomy hemodynamics pain Background Gallstones are a common health issue in advanced countries, affecting approximately 10–15% of the general population. Laparoscopic cholecystectomy is considered the gold standard surgical procedure for symptomatic gallstones ( 1 , 2 ). This treatment method has a short hospital stay and allows for a quick return to daily activities ( 3 ). Laparoscopic cholecystectomy has significantly improved surgical outcomes compared to traditional methods, reducing postoperative pain and recovery time. However, anesthesia management during laparoscopic surgeries presents challenges due to the significant changes in hemodynamics caused by factors such as pneumoperitoneum, patient positioning, anesthesia, and CO2 absorption ( 4 ). The creation of pneumoperitoneum (increased intrabdominal pressure) leads to increased plasma renin activity, plasma norepinephrine, and epinephrine levels, as well as activation of the renin-angiotensin-aldosterone system ( 5 – 7 ). These changes generally result in increased arterial blood pressure, systemic and pulmonary vascular resistance, and reduced cardiac output. However, limited information exists regarding the systemic effects of increased intrabdominal pressure in patients undergoing laparoscopic cholecystectomy. In a study conducted by Avneesh Khare and colleagues in 2017, it was noted that although increased intrabdominal pressure is routinely performed in patients requiring laparoscopic cholecystectomy, there is limited information regarding its systemic effects, especially its impact on patients' blood pressure and hemodynamic changes ( 8 ). This study aims to investigate the effects of increased intrabdominal pressure on blood pressure in laparoscopic cholecystectomy patients. Methods This study was a randomized controlled trial conducted at Ayatollah Kashani Hospital in Shahrekord. It had a two-group design and included a total of 100 patients who met the inclusion criteria and were candidates for laparoscopic cholecystectomy. The inclusion criteria consisted of confirmed ultrasound results indicating gallstones, symptomatic gallbladder disease (painful attacks, history of cholecystitis or pancreatitis associated with gallstones), eligibility for laparoscopic cholecystectomy, ASA class 1–2, and age between 20 and 55 years. The patients provided written informed consent after being explained the objectives and methods of the study. The surgical procedure was performed and the researcher was present in the operating room throughout. All patients fasted for 8 hours prior to the surgery and received fluid maintenance according to the 1-2-4 rule. After entering the operating room, their height and weight were measured and they were assessed for eligibility and absence of exclusion criteria before being enrolled in the study. Upon entering the operating room, the patients were administered intravenous midazolam at a dose of 0.3 mg/kg. The patients were randomly assigned to two groups, A and B, using Balanced Block Randomization. Only the responsible physician (supervisor) was aware of the patient allocation. In the control group, a pressure of 15 was applied to the patient, while in the intervention group, pressures of 5, 10, and 15 were applied. Each patient was assigned a number by the supervisor and recorded in a notebook. For example, patient number 1 was assigned to group A, and patient number 2 was assigned to group B, or vice versa. The blinding method is explained below. The same medications were used for inducing anesthesia and as maintenance for all participating patients in collaboration with the anesthesiologist specialist. The laparoscopic technique was performed using 4 trocars and carbon dioxide gas insufflation.ECG, blood pressure, and pulse oximetry monitoring were performed on the patients. Before anesthesia induction, all patients received 7 cc/kg of Ringer's lactate to expand their crystalloid volume. They were then given 2 micrograms/kg of fentanyl, 2 mg/kg of propofol, and 0.5 mg/kg of atracurium. Afterwards, they were intubated with an appropriately sized endotracheal tube. Once intubated, they were connected to the ventilator with a tidal volume of 8 cc/kg, respiratory rate (RR) of 10, positive end-expiratory pressure (PeeP) of 3, and a ratio of inspiratory time to expiratory time (TI/TE) of 1:2. At time zero, before the start of surgery, blood pressure, heart rate, and arterial oxygen saturation were measured and recorded. All patients were then positioned in the standard American position (using 4 trocars and positioned at a 30-degree reverse Trendelenburg and 30-degree left tilt). CO2 gas insufflation was performed in three stages with pressure levels of 5, 10, and 15 mmHg, each stage lasting 2 minutes. In the control group, only a pressure of 15 mmHg was applied to the patient. After each stage, hemodynamic variables were reassessed. Once the surgery was complete and the surgeon removed the intra-abdominal gas, hemodynamic signs were measured again. According to the vas system, patients were given a pain score during recovery. The data were analyzed using SPSS software, and statistical tests including T-test and Chi-square were employed. Quantitative data were expressed as mean and standard deviation, while qualitative data were expressed as numbers and percentages. Results with p-values less than 0.05 were considered statistically significant. Results This study was conducted on 100 patients, with 50 individuals in the abdominal pressure increase group (intervention) and 50 individuals in the control group (15 mmHg pressure). The majority of the samples in the intervention group were 27 individuals (54%), while in the control group, there were 28 individuals (56%) who were female. The mean and standard deviation of age in the intervention group were 86.6 ± 92.38, and in the control group, it was 54.6 ± 24.37. The two groups were relatively similar in terms of gender, age, height, weight, and body mass index (BMI) (P < 0.05). Table 1 shows the demographic variables in the study groups, with quantitative variables presented as standard deviation ± mean and qualitative variables presented as percentages. Table 1 Demographic variables in the studied groups. Variable Groups P-value Intervention (50 = n) Control (50 = n) Age (years) 38.92 ± 6.86 37.24 ± 6.54 0.218 Height (cm) 169.76 ± 8.46 167.20 ± 9.34 0.109 Weight (kg) 72.26 ± 13.02 71.74 ± 13.97 0.915 Body mass index (BMI) 25.17 ± 4.81 25.74 ± 5 0.313 Gender Male 23 (46%) 22 (44%) 0.841 Female 28 (56%) 27 (54%) Table 2 displays the mean and standard deviation of heart rate and arterial blood oxygen levels in the two groups at different time points. The mean heart rate at zero and 20 minutes did not show a significant difference between the two groups. However, in other time points, the mean heart rate in the intervention group was significantly lower than the control group (P < 0.001). The mean arterial blood oxygen levels did not show a significant difference between the intervention and control groups (P = 0.721). Additionally, the mean arterial blood oxygen levels at each time point did not show a significant difference between the control and intervention groups (P > 0.05). Table 2 Mean and standard deviation of heart rate and arterial blood oxygen in two groups of patients at the investigated times. Times Groups Intervention (mean ± SD) Control (mean ± SD) Heart rate immediately (time zero) 92.44 ± 7.93 91.16 ± 12.62 20 minutes 88.80 ± 8.20 92.88 ± 12.32 40 minutes 88.52 ± 7.57 98.02 ± 15.65 60 minutes 87.98 ± 7.35 100/16 ± 15/07 90 minutes 86.11 ± 7.41 97.96 ± 14.23 Arterial blood oxygen immediately (time zero) 96.62 ± 1.32 96.56 ± 1.29 20 minutes 97.02 ± 1.46 96.80 ± 1.41 40 minutes 96.90 ± 1.43 96.72 ± 1.35 60 minutes 96.82 ± 1.60 96.80 ± 1.59 90 minutes 96.76 ± 1.66 96.89 ± 1.66 Table 3 displays Mean and standard deviation of systolic, diastolic and arterial blood pressure in the two groups of patients at the investigated times. The mean systolic blood pressure in the intervention group is significantly lower than the control group (p-value < 0.001). The mean systolic blood pressure during the examined time points shows that it is significantly lower at time zero compared to times 20, 40, 60, and 90 (p-value < 0.001). The mean systolic blood pressure in the intervention group is significantly lower than the control group at each examined time point (p-value < 0.001). The mean systolic blood pressure at time zero does not show a significant difference between the two groups, but at times 20, 40, 60, and 90, the mean systolic blood pressure in the intervention group is significantly lower than the control group (p-value < 0.001). The mean diastolic blood pressure in the intervention group is significantly lower than the control group (p-value < 0.001). The mean diastolic blood pressure at time zero is significantly lower than times 20, 40, 60, and 90 (p-value < 0.001). There is no significant difference in the mean diastolic blood pressure at time zero between the two groups, but at times 20, 40, 60, and 90, the mean diastolic blood pressure in the intervention group is significantly lower than the control group (p-value < 0.001). The mean arterial blood pressure in the intervention group is significantly lower than the control group (p-value < 0.001). The mean arterial blood pressure at time zero is significantly lower than times 20, 40, 60, and 90 (p-value 0.05), but at times 20, 40, 60, and 90, the mean arterial blood pressure in the intervention group is significantly lower than the control group (p-value < 0.001). Table 3 Mean and standard deviation of systolic, diastolic and arterial blood pressure in the two groups of patients at the investigated times. Times Groups Intervention (mean ± SD) Control (mean ± SD) Arterial blood pressure immediately (time zero) 95.83 ± 6.77 97.80 ± 9.46 20 minutes 98.24 ± 7.44 107.46 ± 13.29 40 minutes 100.87 ± 7.74 111.09 ± 13.54 60 minutes 97.38 ± 7.42 108.69 ± 13.40 90 minutes 96.42 ± 8.16 105.19 ± 13.99 Systolic blood pressure immediately (time zero) 124.04 ± 7.16 125.68 ± 9.79 20 minutes 126.28 ± 7.45 136.14 ± 13.68 40 minutes 127.64 ± 7.76 137.66 ± 13.51 60 minutes 127.26 ± 7.55 138.70 ± 14.10 90 minutes 123.40 ± 8.15 133.00 ± 14.22 Diastolic blood pressure immediately (time zero) 81.72 ± 6.67 83.86 ± 9.42 20 minutes 84.22 ± 7.83 93.12 ± 13.16 40 minutes 87.48 ± 8.22 97.80 ± 13.64 60 minutes 82.44 ± 7.39 93.68 ± 13.21 90 minutes 82.93 ± 8.41 91.28 ± 14.14 Table 4 compares the average pain scores, duration of hospitalization, and prescription pethidine amount between two groups of patients. The intervention group has a significantly lower mean pain score than the control group (p-value < 0.001). Additionally, the mean pain score at 20 minutes after recovery is significantly higher compared to 40 and 60 minutes after recovery (p < 0.001). Furthermore, the intervention group has significantly lower mean pain scores at both 20 and 40 minutes after recovery when compared to the control group (p 0.05). The results of the independent t-test show that there is no significant difference in the average duration of hospitalization between the intervention and control groups (P > 0.05). Furthermore, the intervention group has significantly lower levels of prescribed medication compared to the control group (P < 0.001). Table 4 Pain scores, duration of hospitalization, and prescription pethidine amount between two groups of patients. Times Groups Intervention (mean ± SD) Control (mean ± SD) Pain score 20 minutes 5.04 ± 1.45 6.68 ± 1.98 40 minutes 4.22 ± 1.03 5.36 ± 1.92 60 minutes 3.78 ± 1.32 4.08 ± 1.82 Duration of hospitalization Recovery Time (in minutes) 84.90 ± 12.75 89.20 ± 10.46 Prescription pethidine amount Pethidine (mg) 8.25 ± 12.78 21.00 ± 16.64 Discussion The aim of this study was to examine the effects of increased intra-abdominal pressure on blood pressure in patients undergoing laparoscopic cholecystectomy. Our findings showed that at minute 20, the intervention group had significantly lower mean heart rate, blood pressure (systolic, diastolic, and mean arterial pressure) compared to the control group. The intervention group maintained stability in heart rate and blood pressure from minute 20 to minute 90, while the control group experienced a statistically significant increase in heart rate and blood pressure during surgery. The intervention group also had a significantly lower less pain at 20 and 40 minutes during recovery, and a lower mean administration of analgesic (pethidine) compared to the control group. However, there were no statistically significant differences between the two groups in terms of arterial blood oxygen saturation during surgery, duration of recovery room stay. Umar et al. conducted a study on the impact of increased intra-abdominal pressure on hemodynamic changes in patients. The study included three groups with varying levels of intra-abdominal pressure. Parameters such as heart rate, blood pressure, and carbon dioxide levels were measured at different intervals during and after CO2 insufflation. The patients were placed in a reverse Trendelenburg position during surgery, and the results were analyzed using statistical tests. The study found that the mean heart rate increased immediately after CO2 insufflation and then decreased until 10 minutes after insufflation. Group III had significantly higher heart rates compared to the other groups at later time points. Systolic blood pressure and mean arterial pressure were also affected by the intra-abdominal pressure, with significant differences observed between groups. The study concluded that laparoscopic cholecystectomy causes significant hemodynamic changes, mainly related to the cardiovascular system. Higher intra-abdominal pressure is associated with greater fluctuations in hemodynamic parameters, but maintaining lower pressure reduces the adverse effects. Gradually increasing the pressure allows the body to adapt and leads to greater stability in vital signs during surgery ( 9 ). Our study's findings align with these results and demonstrate that allowing the body to adapt to increased intra-abdominal pressure and gradually increasing the pressure leads to greater stability in vital signs during surgery. A study conducted by Korkmaz et al. aimed to investigate the changes in blood flow during laparoscopic cholecystectomy with and without the use of CO2 insufflation. The gasless laparoscopic method involves using an electromechanical retraction system to lift the abdominal wall. The study included a total of 31 patients with gallbladder stones, with 20 undergoing laparoscopic cholecystectomy with gas insufflation and 11 without gas insufflation. The researchers assessed various hemodynamic parameters such as mean arterial pressure, heart rate, systemic vascular resistance index, cardiac index (CI), ejection fraction (EF), and stroke indices (SI). In the group that received gas insufflation, significant changes were observed in CI, EF, and SI after insufflation, compared to the values before pneumoperitoneum. However, in the gasless group, only a slight change in SI was observed, which was not statistically significant. In conclusion, gasless laparoscopy has minimal effects on hemodynamic parameters in patients, suggesting that gas insufflation should be performed selectively rather than in all cases ( 10 ). Furthermore, our study demonstrated that insufflating a pressure of 15 mmHg in the control group resulted in a significant destabilization of hemodynamic stability, as manifested by a notable increase in heart rate and blood pressure during surgery. The stepwise increase in intra-abdominal pressure during gas insufflation significantly contributes to maintaining stable vital signs in patients, providing a reliable solution for managing unstable vital signs during surgery. Another study conducted by Sood et al. aimed to examine how gas insufflation affects the hemodynamics and catecholamine levels of patients. The study included nine patients who were randomly assigned to two groups: Group A, which maintained an intra-abdominal pressure of 15 mmHg, and Group B, which maintained a pressure of 8–10 mmHg. The levels of norepinephrine and epinephrine in the blood were measured at different stages of the operation. Hemodynamic variables were also recorded. The introduction of carboperitoneum resulted in an increase in heart rate and mean arterial pressure (MAP), although the increase was not statistically significant. The level of norepinephrine in Group A showed a significant increase compared to Group B. Surgical manipulation led to a considerable increase in MAP and norepinephrine levels in Group A. In conclusion, maintaining a lower intra-abdominal pressure of 8–10 mmHg reduces catecholamine release and hemodynamic fluctuations ( 11 ). Therefore, based on the findings of this study, it can be inferred that gradually increasing the intra-abdominal pressure may lead to a reduction in catecholamine release and hemodynamic fluctuations. However, further studies focusing on the pathophysiology of these findings are necessary. A study by Rishimani et al. examined the effects of high and low intra-abdominal pressures on hemodynamic changes in patients undergoing laparoscopic cholecystectomy. The study included thirty-three patients, with varying ASA classifications. Measurements of mean arterial pressure (MAP), heart rate (HR), arterial oxygen saturation (SaO2), airway pressure (AWP), and end-tidal carbon dioxide (ETCO2) were taken at different stages of the operation. In T2, when the intra-abdominal pressure was 14 mmHg, there was a significant increase in MAP, AWP, and ETCO2 compared to the initial measurement (T1). In T3, when the pressure was reduced to 6 mmHg or less, there was still a significant increase in MAP, AWP, and ETCO2 compared to T1. However, HR and SaO2 did not show significant changes. Therefore, lowering the insufflation pressure may be beneficial for patients with limited cardiopulmonary reserve, particularly during longer surgical procedures ( 12 ). While the study design mentioned is not identical to ours, it can be inferred that the magnitude and method of insufflation significantly impact the hemodynamic parameters of patients. Future studies should explore and compare different approaches to determine the optimal method and pressure for insufflation. Kim et al. conducted a study to examine how different levels of carbon dioxide gas pressure and the injection of normal saline into the abdomen affect shoulder pain after laparoscopic cholecystectomy. The study included 109 patients who were divided into three groups: one group received carbon dioxide gas at a pressure of 14 mmHg, another group received carbon dioxide gas at a pressure of 10 mmHg, and the third group received carbon dioxide gas at 10 mmHg along with intraperitoneal normal saline. Shoulder pain levels were assessed at various time points after surgery. The findings showed that the second and third groups had lower levels of pain compared to the first group, with no significant difference between the second and third groups observed ( 13 ). This study, although different in design, indicated that the method of gas insufflation also affects postoperative pain. In our study, we found that gradual insufflation of CO2 significantly improved postoperative pain and reduced the need for pain medication. In a study by Berberoglu, the effect of different rates of carbon dioxide gas insufflation on shoulder pain in patients undergoing laparoscopic surgery was investigated. The study included seventy-six patients who were divided into two groups: one group received carbon dioxide gas at a flow rate of 5 L/min, and the other group received carbon dioxide gas at a flow rate of 5.7 L/min. The patients were evaluated for pain on the third day after surgery. The findings showed that the second group had a significantly lower average pain score compared to the first group ( 14 ). These findings are consistent with our study, which also showed that gentle insufflation of CO2 significantly improved postoperative pain. Sarli conducted a study to examine the effect of different levels of carbon dioxide gas pressure on shoulder pain after laparoscopic cholecystectomy. The study included 90 patients who were divided into two randomized groups: one group had a intra-abdominal pressure (IAP) of 9 mmHg and the other group had an IAP of 13 mmHg. Shoulder pain levels were assessed at various time points after surgery using the VAS questionnaire. The findings indicated significantly lower average pain scores in the low-pressure gas group compared to the other group ( 15 ). Although our study did not involve lower pressure levels, gradual insufflation had similar effects to lower pressure insufflation, resulting in improved postoperative pain and reduced need for pain medication. In a review study conducted by Rothman et al. in 2014, a total of 50 journals were examined. Out of these, 42 journals were excluded and 8 were included for analysis. In total, 578 patients were included in the analysis. The overall scientific quality of the studies was deemed weak. The study found that the use of intra-abdominal pressure had a positive impact on physical performance but negatively affected lung function. However, its effects on postoperative pain were still uncertain. Due to the weak evidence and poor quality of the studies, drawing comprehensive conclusions proved challenging. The study suggests that high-quality randomized clinical trials with specific methodologies are necessary ( 16 ). Based on the findings of this study and our own, it can be concluded that different gas insufflation methods lead to varying outcomes in terms of postoperative pain. This highlights the need for further studies and comparisons to determine the optimal method and pressure required for insufflation. A study conducted in 2016 by Campos-Muñoz MA and colleagues aimed to investigate the relationship between intra-abdominal pressure and postoperative pain. Thirty-seven patients were included in the study, all of whom underwent surgery with prior measurement of intra-abdominal pressure. Based on the results of the anatomopathology, the patients were divided into two groups: those with acute abdominal inflammatory process (28 individuals, the case group) and those without evidence of acute abdominal inflammation (9 individuals, the control group). In the case group, 100% of the patients showed high intra-abdominal pressure with AP = 0.01 (OR = 5, 95% CI = 2.578–9.699). The mean intra-abdominal pressure was 11.46 in the case group and 9.2 in the control group. The study concluded that abdominal pain requiring surgical intervention is directly related to intra-abdominal pressure greater than 5 mmHg and related breathing rate ( 17 ). In our study, it was also found that a sudden increase in intra-abdominal pressure to 15 mmHg significantly increases postoperative pain in patients. Mario Schietroma et al. conducted a study to investigate the effect of intra-abdominal pressure on pain and the inflammatory process after adrenalectomy. The study included 51 patients who were randomly assigned to either the standard pressure group (12–14 mmHg) or the low-pressure group (6–8 mmHg) during pneumoperitoneum. Various markers of inflammation and pain were examined, including white blood cells, lymphocyte population, human leukocyte antigens, neutrophil elastase, interleukin levels, and C-reactive protein. The study found significantly higher concentrations of inflammatory markers in the standard pressure group compared to the low-pressure group. Additionally, there were significant changes in antigen expression on monocyte surfaces in the standard pressure group, indicating decreased antigen expression. In conclusion, reducing pneumoperitoneum pressure to 6–8 mmHg during laparotomy resulted in reduced inflammatory response and postoperative pain in patients. ( 18 ). Therefore, based on the findings of this study and our study, it can be inferred that the method, speed, and level of pressure have significant effects on different variables and biomarkers, leading to changes or stability in hemodynamics and postoperative pain. Conclusion Our study revealed that the mean heart rate, blood pressure (systolic, diastolic, and mean arterial pressure), mean pain score, and administration of analgesics (pethidine) during recovery were significantly lower in the intervention group compared to the control group. However, there were no statistically significant differences in arterial blood oxygen saturation during surgery, duration of recovery between the two study groups. Therefore, for all patients requiring cholecystectomy, intra-abdominal pressure should be increased using the method obtained in our study (gradual insufflation) to achieve hemodynamic stability during surgery and reduce postoperative pain, leading to improved quality of care. Additionally, by reducing pain, patients experience less discomfort, reduced need for cardiac oxygen, and consequently lower risk of myocardial ischemia, decreased prolonged immobility, decreased suppression of the immune system, reduced risk of hyperglycemia, faster wound healing, reduced risk of atelectasis, and more. Declarations Ethics Approval and Consent to Participate The studies involving human participants were reviewed and approved by Shahrekord University of medical sciences (IR.SKUMS.REC.1400.117). The patients/participants provided their written informed consent to participate in this study. Acknowledgment The authors thank all the volunteers who participated in the study. Funding This research received no external funding. Conflict of interest 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. References Kwon YJ, Ahn BK, Park HK, Lee KS, Lee KG. 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Minimally Invasive Surgery. 2014;2014. Rothman JP, Gunnarsson U, Bisgaard T. Abdominal binders may reduce pain and improve physical function after major abdominal surgery-a systematic review. database. 1966;2013. Campos-Muñoz MA, Villarreal-Ríos E, Chimal-Torres M, Pozas-Medina JA. Intra-abdominal pressure as a surgery predictor in patients with acute abdominal pain. Revista Médica del Instituto Mexicano del Seguro Social. 2016;54(3):280-5. Schietroma M, Pessia B, Stifini D, Lancione L, Carlei F, Cecilia EM, et al. Effects of low and standard intra-abdominal pressure on systemic inflammation and immune response in laparoscopic adrenalectomy: a prospective randomised study. Journal of Minimal Access Surgery. 2016;12(2):109. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4601648","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":319752504,"identity":"42984007-1d23-4a65-8d48-21aaca4a28b9","order_by":0,"name":"Mohamadreza Abedinzade","email":"","orcid":"","institution":"Shahrekord University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Mohamadreza","middleName":"","lastName":"Abedinzade","suffix":""},{"id":319752509,"identity":"a3303c50-305f-40c9-bece-04395dfaaf83","order_by":1,"name":"Negin Taghavi","email":"","orcid":"","institution":"Shahrekord University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Negin","middleName":"","lastName":"Taghavi","suffix":""},{"id":319752512,"identity":"0867d294-9585-47d1-979d-08738a735b9d","order_by":2,"name":"Nafise Mohamadi Farsani","email":"data:image/png;base64,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","orcid":"","institution":"Shahrekord University of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Nafise","middleName":"Mohamadi","lastName":"Farsani","suffix":""}],"badges":[],"createdAt":"2024-06-18 18:14:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4601648/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4601648/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":60820398,"identity":"e911369c-c7f5-4b1b-acd3-73d0c7e9a8cb","added_by":"auto","created_at":"2024-07-22 12:55:09","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":550260,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4601648/v1/309a9163-904b-4a55-a859-f0f520175644.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Evaluation of the effects of gradual increases in intra-abdominal pressure on blood pressure in a patient undergoing laparoscopic cholecystectomy.","fulltext":[{"header":"Background","content":"\u003cp\u003eGallstones are a common health issue in advanced countries, affecting approximately 10\u0026ndash;15% of the general population. Laparoscopic cholecystectomy is considered the gold standard surgical procedure for symptomatic gallstones (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). This treatment method has a short hospital stay and allows for a quick return to daily activities (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eLaparoscopic cholecystectomy has significantly improved surgical outcomes compared to traditional methods, reducing postoperative pain and recovery time. However, anesthesia management during laparoscopic surgeries presents challenges due to the significant changes in hemodynamics caused by factors such as pneumoperitoneum, patient positioning, anesthesia, and CO2 absorption (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). The creation of pneumoperitoneum (increased intrabdominal pressure) leads to increased plasma renin activity, plasma norepinephrine, and epinephrine levels, as well as activation of the renin-angiotensin-aldosterone system (\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). These changes generally result in increased arterial blood pressure, systemic and pulmonary vascular resistance, and reduced cardiac output. However, limited information exists regarding the systemic effects of increased intrabdominal pressure in patients undergoing laparoscopic cholecystectomy.\u003c/p\u003e \u003cp\u003eIn a study conducted by Avneesh Khare and colleagues in 2017, it was noted that although increased intrabdominal pressure is routinely performed in patients requiring laparoscopic cholecystectomy, there is limited information regarding its systemic effects, especially its impact on patients' blood pressure and hemodynamic changes (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). This study aims to investigate the effects of increased intrabdominal pressure on blood pressure in laparoscopic cholecystectomy patients.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis study was a randomized controlled trial conducted at Ayatollah Kashani Hospital in Shahrekord. It had a two-group design and included a total of 100 patients who met the inclusion criteria and were candidates for laparoscopic cholecystectomy. The inclusion criteria consisted of confirmed ultrasound results indicating gallstones, symptomatic gallbladder disease (painful attacks, history of cholecystitis or pancreatitis associated with gallstones), eligibility for laparoscopic cholecystectomy, ASA class 1\u0026ndash;2, and age between 20 and 55 years.\u003c/p\u003e \u003cp\u003e The patients provided written informed consent after being explained the objectives and methods of the study. The surgical procedure was performed and the researcher was present in the operating room throughout. All patients fasted for 8 hours prior to the surgery and received fluid maintenance according to the 1-2-4 rule. After entering the operating room, their height and weight were measured and they were assessed for eligibility and absence of exclusion criteria before being enrolled in the study. Upon entering the operating room, the patients were administered intravenous midazolam at a dose of 0.3 mg/kg.\u003c/p\u003e \u003cp\u003eThe patients were randomly assigned to two groups, A and B, using Balanced Block Randomization. Only the responsible physician (supervisor) was aware of the patient allocation. In the control group, a pressure of 15 was applied to the patient, while in the intervention group, pressures of 5, 10, and 15 were applied. Each patient was assigned a number by the supervisor and recorded in a notebook. For example, patient number 1 was assigned to group A, and patient number 2 was assigned to group B, or vice versa. The blinding method is explained below.\u003c/p\u003e \u003cp\u003eThe same medications were used for inducing anesthesia and as maintenance for all participating patients in collaboration with the anesthesiologist specialist. The laparoscopic technique was performed using 4 trocars and carbon dioxide gas insufflation.ECG, blood pressure, and pulse oximetry monitoring were performed on the patients. Before anesthesia induction, all patients received 7 cc/kg of Ringer's lactate to expand their crystalloid volume. They were then given 2 micrograms/kg of fentanyl, 2 mg/kg of propofol, and 0.5 mg/kg of atracurium. Afterwards, they were intubated with an appropriately sized endotracheal tube. Once intubated, they were connected to the ventilator with a tidal volume of 8 cc/kg, respiratory rate (RR) of 10, positive end-expiratory pressure (PeeP) of 3, and a ratio of inspiratory time to expiratory time (TI/TE) of 1:2.\u003c/p\u003e \u003cp\u003eAt time zero, before the start of surgery, blood pressure, heart rate, and arterial oxygen saturation were measured and recorded. All patients were then positioned in the standard American position (using 4 trocars and positioned at a 30-degree reverse Trendelenburg and 30-degree left tilt). CO2 gas insufflation was performed in three stages with pressure levels of 5, 10, and 15 mmHg, each stage lasting 2 minutes. In the control group, only a pressure of 15 mmHg was applied to the patient. After each stage, hemodynamic variables were reassessed. Once the surgery was complete and the surgeon removed the intra-abdominal gas, hemodynamic signs were measured again. According to the vas system, patients were given a pain score during recovery.\u003c/p\u003e \u003cp\u003eThe data were analyzed using SPSS software, and statistical tests including T-test and Chi-square were employed. Quantitative data were expressed as mean and standard deviation, while qualitative data were expressed as numbers and percentages. Results with p-values less than 0.05 were considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThis study was conducted on 100 patients, with 50 individuals in the abdominal pressure increase group (intervention) and 50 individuals in the control group (15 mmHg pressure). The majority of the samples in the intervention group were 27 individuals (54%), while in the control group, there were 28 individuals (56%) who were female. The mean and standard deviation of age in the intervention group were 86.6\u0026thinsp;\u0026plusmn;\u0026thinsp;92.38, and in the control group, it was 54.6\u0026thinsp;\u0026plusmn;\u0026thinsp;24.37. The two groups were relatively similar in terms of gender, age, height, weight, and body mass index (BMI) (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the demographic variables in the study groups, with quantitative variables presented as standard deviation\u0026thinsp;\u0026plusmn;\u0026thinsp;mean and qualitative variables presented as percentages.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic variables in the studied groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eGroups\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIntervention\u003c/p\u003e \u003cp\u003e(50\u0026thinsp;=\u0026thinsp;n)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003cp\u003e(50\u0026thinsp;=\u0026thinsp;n)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge (years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38.92\u0026thinsp;\u0026plusmn;\u0026thinsp;6.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37.24\u0026thinsp;\u0026plusmn;\u0026thinsp;6.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.218\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHeight (cm)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e169.76\u0026thinsp;\u0026plusmn;\u0026thinsp;8.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e167.20\u0026thinsp;\u0026plusmn;\u0026thinsp;9.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.109\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eWeight (kg)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72.26\u0026thinsp;\u0026plusmn;\u0026thinsp;13.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e71.74\u0026thinsp;\u0026plusmn;\u0026thinsp;13.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.915\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBody mass index (BMI)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.17\u0026thinsp;\u0026plusmn;\u0026thinsp;4.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25.74\u0026thinsp;\u0026plusmn;\u0026thinsp;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.313\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eGender\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMale\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (46%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22 (44%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.841\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eFemale\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (56%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27 (54%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e displays the mean and standard deviation of heart rate and arterial blood oxygen levels in the two groups at different time points. The mean heart rate at zero and 20 minutes did not show a significant difference between the two groups. However, in other time points, the mean heart rate in the intervention group was significantly lower than the control group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The mean arterial blood oxygen levels did not show a significant difference between the intervention and control groups (P\u0026thinsp;=\u0026thinsp;0.721). Additionally, the mean arterial blood oxygen levels at each time point did not show a significant difference between the control and intervention groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMean and standard deviation of heart rate and arterial blood oxygen in two groups of patients at the investigated times.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eTimes\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eGroups\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIntervention\u003c/p\u003e \u003cp\u003e(mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003cp\u003e(mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eHeart rate\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eimmediately (time zero)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e92.44\u0026thinsp;\u0026plusmn;\u0026thinsp;7.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e91.16\u0026thinsp;\u0026plusmn;\u0026thinsp;12.62\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e20 minutes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e88.80\u0026thinsp;\u0026plusmn;\u0026thinsp;8.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e92.88\u0026thinsp;\u0026plusmn;\u0026thinsp;12.32\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e40 minutes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e88.52\u0026thinsp;\u0026plusmn;\u0026thinsp;7.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e98.02\u0026thinsp;\u0026plusmn;\u0026thinsp;15.65\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e60 minutes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e87.98\u0026thinsp;\u0026plusmn;\u0026thinsp;7.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100/16\u0026thinsp;\u0026plusmn;\u0026thinsp;15/07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e90 minutes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e86.11\u0026thinsp;\u0026plusmn;\u0026thinsp;7.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e97.96\u0026thinsp;\u0026plusmn;\u0026thinsp;14.23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eArterial blood oxygen\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eimmediately (time zero)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e96.62\u0026thinsp;\u0026plusmn;\u0026thinsp;1.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e96.56\u0026thinsp;\u0026plusmn;\u0026thinsp;1.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e20 minutes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e97.02\u0026thinsp;\u0026plusmn;\u0026thinsp;1.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e96.80\u0026thinsp;\u0026plusmn;\u0026thinsp;1.41\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e40 minutes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e96.90\u0026thinsp;\u0026plusmn;\u0026thinsp;1.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e96.72\u0026thinsp;\u0026plusmn;\u0026thinsp;1.35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e60 minutes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e96.82\u0026thinsp;\u0026plusmn;\u0026thinsp;1.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e96.80\u0026thinsp;\u0026plusmn;\u0026thinsp;1.59\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e90 minutes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e96.76\u0026thinsp;\u0026plusmn;\u0026thinsp;1.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e96.89\u0026thinsp;\u0026plusmn;\u0026thinsp;1.66\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e displays Mean and standard deviation of systolic, diastolic and arterial blood pressure in the two groups of patients at the investigated times. The mean systolic blood pressure in the intervention group is significantly lower than the control group (p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The mean systolic blood pressure during the examined time points shows that it is significantly lower at time zero compared to times 20, 40, 60, and 90 (p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The mean systolic blood pressure in the intervention group is significantly lower than the control group at each examined time point (p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The mean systolic blood pressure at time zero does not show a significant difference between the two groups, but at times 20, 40, 60, and 90, the mean systolic blood pressure in the intervention group is significantly lower than the control group (p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eThe mean diastolic blood pressure in the intervention group is significantly lower than the control group (p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The mean diastolic blood pressure at time zero is significantly lower than times 20, 40, 60, and 90 (p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.001). There is no significant difference in the mean diastolic blood pressure at time zero between the two groups, but at times 20, 40, 60, and 90, the mean diastolic blood pressure in the intervention group is significantly lower than the control group (p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eThe mean arterial blood pressure in the intervention group is significantly lower than the control group (p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The mean arterial blood pressure at time zero is significantly lower than times 20, 40, 60, and 90 (p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The mean arterial blood pressure at time zero does not show a significant difference between the two groups (p-value\u0026thinsp;\u0026gt;\u0026thinsp;0.05), but at times 20, 40, 60, and 90, the mean arterial blood pressure in the intervention group is significantly lower than the control group (p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMean and standard deviation of systolic, diastolic and arterial blood pressure in the two groups of patients at the investigated times.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eTimes\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eGroups\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIntervention\u003c/p\u003e \u003cp\u003e(mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003cp\u003e(mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eArterial blood pressure\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eimmediately (time zero)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e95.83\u0026thinsp;\u0026plusmn;\u0026thinsp;6.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e97.80\u0026thinsp;\u0026plusmn;\u0026thinsp;9.46\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e20 minutes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e98.24\u0026thinsp;\u0026plusmn;\u0026thinsp;7.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e107.46\u0026thinsp;\u0026plusmn;\u0026thinsp;13.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e40 minutes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100.87\u0026thinsp;\u0026plusmn;\u0026thinsp;7.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e111.09\u0026thinsp;\u0026plusmn;\u0026thinsp;13.54\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e60 minutes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e97.38\u0026thinsp;\u0026plusmn;\u0026thinsp;7.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e108.69\u0026thinsp;\u0026plusmn;\u0026thinsp;13.40\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e90 minutes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e96.42\u0026thinsp;\u0026plusmn;\u0026thinsp;8.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e105.19\u0026thinsp;\u0026plusmn;\u0026thinsp;13.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSystolic blood pressure\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eimmediately (time zero)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e124.04\u0026thinsp;\u0026plusmn;\u0026thinsp;7.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e125.68\u0026thinsp;\u0026plusmn;\u0026thinsp;9.79\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e20 minutes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e126.28\u0026thinsp;\u0026plusmn;\u0026thinsp;7.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e136.14\u0026thinsp;\u0026plusmn;\u0026thinsp;13.68\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e40 minutes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e127.64\u0026thinsp;\u0026plusmn;\u0026thinsp;7.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e137.66\u0026thinsp;\u0026plusmn;\u0026thinsp;13.51\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e60 minutes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e127.26\u0026thinsp;\u0026plusmn;\u0026thinsp;7.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e138.70\u0026thinsp;\u0026plusmn;\u0026thinsp;14.10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e90 minutes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e123.40\u0026thinsp;\u0026plusmn;\u0026thinsp;8.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e133.00\u0026thinsp;\u0026plusmn;\u0026thinsp;14.22\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDiastolic blood pressure\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eimmediately (time zero)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e81.72\u0026thinsp;\u0026plusmn;\u0026thinsp;6.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e83.86\u0026thinsp;\u0026plusmn;\u0026thinsp;9.42\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e20 minutes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e84.22\u0026thinsp;\u0026plusmn;\u0026thinsp;7.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e93.12\u0026thinsp;\u0026plusmn;\u0026thinsp;13.16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e40 minutes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e87.48\u0026thinsp;\u0026plusmn;\u0026thinsp;8.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e97.80\u0026thinsp;\u0026plusmn;\u0026thinsp;13.64\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e60 minutes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e82.44\u0026thinsp;\u0026plusmn;\u0026thinsp;7.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e93.68\u0026thinsp;\u0026plusmn;\u0026thinsp;13.21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e90 minutes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e82.93\u0026thinsp;\u0026plusmn;\u0026thinsp;8.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e91.28\u0026thinsp;\u0026plusmn;\u0026thinsp;14.14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e compares the average pain scores, duration of hospitalization, and prescription pethidine amount between two groups of patients. The intervention group has a significantly lower mean pain score than the control group (p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Additionally, the mean pain score at 20 minutes after recovery is significantly higher compared to 40 and 60 minutes after recovery (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Furthermore, the intervention group has significantly lower mean pain scores at both 20 and 40 minutes after recovery when compared to the control group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). However, there is no significant difference in mean pain scores between the two groups at 60 minutes (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The results of the independent t-test show that there is no significant difference in the average duration of hospitalization between the intervention and control groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Furthermore, the intervention group has significantly lower levels of prescribed medication compared to the control group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePain scores, duration of hospitalization, and prescription pethidine amount between two groups of patients.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eTimes\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eGroups\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIntervention\u003c/p\u003e \u003cp\u003e(mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003cp\u003e(mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003ePain score\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e20 minutes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.04\u0026thinsp;\u0026plusmn;\u0026thinsp;1.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.68\u0026thinsp;\u0026plusmn;\u0026thinsp;1.98\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e40 minutes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.22\u0026thinsp;\u0026plusmn;\u0026thinsp;1.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.36\u0026thinsp;\u0026plusmn;\u0026thinsp;1.92\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e60 minutes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.78\u0026thinsp;\u0026plusmn;\u0026thinsp;1.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.08\u0026thinsp;\u0026plusmn;\u0026thinsp;1.82\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDuration of hospitalization\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRecovery Time (in minutes)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e84.90\u0026thinsp;\u0026plusmn;\u0026thinsp;12.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e89.20\u0026thinsp;\u0026plusmn;\u0026thinsp;10.46\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePrescription pethidine amount\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePethidine (mg)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.25\u0026thinsp;\u0026plusmn;\u0026thinsp;12.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.00\u0026thinsp;\u0026plusmn;\u0026thinsp;16.64\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe aim of this study was to examine the effects of increased intra-abdominal pressure on blood pressure in patients undergoing laparoscopic cholecystectomy. Our findings showed that at minute 20, the intervention group had significantly lower mean heart rate, blood pressure (systolic, diastolic, and mean arterial pressure) compared to the control group. The intervention group maintained stability in heart rate and blood pressure from minute 20 to minute 90, while the control group experienced a statistically significant increase in heart rate and blood pressure during surgery. The intervention group also had a significantly lower less pain at 20 and 40 minutes during recovery, and a lower mean administration of analgesic (pethidine) compared to the control group. However, there were no statistically significant differences between the two groups in terms of arterial blood oxygen saturation during surgery, duration of recovery room stay.\u003c/p\u003e \u003cp\u003eUmar et al. conducted a study on the impact of increased intra-abdominal pressure on hemodynamic changes in patients. The study included three groups with varying levels of intra-abdominal pressure. Parameters such as heart rate, blood pressure, and carbon dioxide levels were measured at different intervals during and after CO2 insufflation. The patients were placed in a reverse Trendelenburg position during surgery, and the results were analyzed using statistical tests. The study found that the mean heart rate increased immediately after CO2 insufflation and then decreased until 10 minutes after insufflation. Group III had significantly higher heart rates compared to the other groups at later time points. Systolic blood pressure and mean arterial pressure were also affected by the intra-abdominal pressure, with significant differences observed between groups. The study concluded that laparoscopic cholecystectomy causes significant hemodynamic changes, mainly related to the cardiovascular system. Higher intra-abdominal pressure is associated with greater fluctuations in hemodynamic parameters, but maintaining lower pressure reduces the adverse effects. Gradually increasing the pressure allows the body to adapt and leads to greater stability in vital signs during surgery (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Our study's findings align with these results and demonstrate that allowing the body to adapt to increased intra-abdominal pressure and gradually increasing the pressure leads to greater stability in vital signs during surgery.\u003c/p\u003e \u003cp\u003eA study conducted by Korkmaz et al. aimed to investigate the changes in blood flow during laparoscopic cholecystectomy with and without the use of CO2 insufflation. The gasless laparoscopic method involves using an electromechanical retraction system to lift the abdominal wall. The study included a total of 31 patients with gallbladder stones, with 20 undergoing laparoscopic cholecystectomy with gas insufflation and 11 without gas insufflation. The researchers assessed various hemodynamic parameters such as mean arterial pressure, heart rate, systemic vascular resistance index, cardiac index (CI), ejection fraction (EF), and stroke indices (SI). In the group that received gas insufflation, significant changes were observed in CI, EF, and SI after insufflation, compared to the values before pneumoperitoneum. However, in the gasless group, only a slight change in SI was observed, which was not statistically significant. In conclusion, gasless laparoscopy has minimal effects on hemodynamic parameters in patients, suggesting that gas insufflation should be performed selectively rather than in all cases (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Furthermore, our study demonstrated that insufflating a pressure of 15 mmHg in the control group resulted in a significant destabilization of hemodynamic stability, as manifested by a notable increase in heart rate and blood pressure during surgery. The stepwise increase in intra-abdominal pressure during gas insufflation significantly contributes to maintaining stable vital signs in patients, providing a reliable solution for managing unstable vital signs during surgery.\u003c/p\u003e \u003cp\u003eAnother study conducted by Sood et al. aimed to examine how gas insufflation affects the hemodynamics and catecholamine levels of patients. The study included nine patients who were randomly assigned to two groups: Group A, which maintained an intra-abdominal pressure of 15 mmHg, and Group B, which maintained a pressure of 8\u0026ndash;10 mmHg. The levels of norepinephrine and epinephrine in the blood were measured at different stages of the operation. Hemodynamic variables were also recorded. The introduction of carboperitoneum resulted in an increase in heart rate and mean arterial pressure (MAP), although the increase was not statistically significant. The level of norepinephrine in Group A showed a significant increase compared to Group B. Surgical manipulation led to a considerable increase in MAP and norepinephrine levels in Group A. In conclusion, maintaining a lower intra-abdominal pressure of 8\u0026ndash;10 mmHg reduces catecholamine release and hemodynamic fluctuations (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Therefore, based on the findings of this study, it can be inferred that gradually increasing the intra-abdominal pressure may lead to a reduction in catecholamine release and hemodynamic fluctuations. However, further studies focusing on the pathophysiology of these findings are necessary.\u003c/p\u003e \u003cp\u003eA study by Rishimani et al. examined the effects of high and low intra-abdominal pressures on hemodynamic changes in patients undergoing laparoscopic cholecystectomy. The study included thirty-three patients, with varying ASA classifications. Measurements of mean arterial pressure (MAP), heart rate (HR), arterial oxygen saturation (SaO2), airway pressure (AWP), and end-tidal carbon dioxide (ETCO2) were taken at different stages of the operation. In T2, when the intra-abdominal pressure was 14 mmHg, there was a significant increase in MAP, AWP, and ETCO2 compared to the initial measurement (T1). In T3, when the pressure was reduced to 6 mmHg or less, there was still a significant increase in MAP, AWP, and ETCO2 compared to T1. However, HR and SaO2 did not show significant changes. Therefore, lowering the insufflation pressure may be beneficial for patients with limited cardiopulmonary reserve, particularly during longer surgical procedures (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). While the study design mentioned is not identical to ours, it can be inferred that the magnitude and method of insufflation significantly impact the hemodynamic parameters of patients. Future studies should explore and compare different approaches to determine the optimal method and pressure for insufflation.\u003c/p\u003e \u003cp\u003eKim et al. conducted a study to examine how different levels of carbon dioxide gas pressure and the injection of normal saline into the abdomen affect shoulder pain after laparoscopic cholecystectomy. The study included 109 patients who were divided into three groups: one group received carbon dioxide gas at a pressure of 14 mmHg, another group received carbon dioxide gas at a pressure of 10 mmHg, and the third group received carbon dioxide gas at 10 mmHg along with intraperitoneal normal saline. Shoulder pain levels were assessed at various time points after surgery. The findings showed that the second and third groups had lower levels of pain compared to the first group, with no significant difference between the second and third groups observed (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). This study, although different in design, indicated that the method of gas insufflation also affects postoperative pain. In our study, we found that gradual insufflation of CO2 significantly improved postoperative pain and reduced the need for pain medication.\u003c/p\u003e \u003cp\u003eIn a study by Berberoglu, the effect of different rates of carbon dioxide gas insufflation on shoulder pain in patients undergoing laparoscopic surgery was investigated. The study included seventy-six patients who were divided into two groups: one group received carbon dioxide gas at a flow rate of 5 L/min, and the other group received carbon dioxide gas at a flow rate of 5.7 L/min. The patients were evaluated for pain on the third day after surgery. The findings showed that the second group had a significantly lower average pain score compared to the first group (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). These findings are consistent with our study, which also showed that gentle insufflation of CO2 significantly improved postoperative pain.\u003c/p\u003e \u003cp\u003eSarli conducted a study to examine the effect of different levels of carbon dioxide gas pressure on shoulder pain after laparoscopic cholecystectomy. The study included 90 patients who were divided into two randomized groups: one group had a intra-abdominal pressure (IAP) of 9 mmHg and the other group had an IAP of 13 mmHg. Shoulder pain levels were assessed at various time points after surgery using the VAS questionnaire. The findings indicated significantly lower average pain scores in the low-pressure gas group compared to the other group (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Although our study did not involve lower pressure levels, gradual insufflation had similar effects to lower pressure insufflation, resulting in improved postoperative pain and reduced need for pain medication.\u003c/p\u003e \u003cp\u003eIn a review study conducted by Rothman et al. in 2014, a total of 50 journals were examined. Out of these, 42 journals were excluded and 8 were included for analysis. In total, 578 patients were included in the analysis. The overall scientific quality of the studies was deemed weak. The study found that the use of intra-abdominal pressure had a positive impact on physical performance but negatively affected lung function. However, its effects on postoperative pain were still uncertain. Due to the weak evidence and poor quality of the studies, drawing comprehensive conclusions proved challenging. The study suggests that high-quality randomized clinical trials with specific methodologies are necessary (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Based on the findings of this study and our own, it can be concluded that different gas insufflation methods lead to varying outcomes in terms of postoperative pain. This highlights the need for further studies and comparisons to determine the optimal method and pressure required for insufflation.\u003c/p\u003e \u003cp\u003eA study conducted in 2016 by Campos-Mu\u0026ntilde;oz MA and colleagues aimed to investigate the relationship between intra-abdominal pressure and postoperative pain. Thirty-seven patients were included in the study, all of whom underwent surgery with prior measurement of intra-abdominal pressure. Based on the results of the anatomopathology, the patients were divided into two groups: those with acute abdominal inflammatory process (28 individuals, the case group) and those without evidence of acute abdominal inflammation (9 individuals, the control group). In the case group, 100% of the patients showed high intra-abdominal pressure with AP\u0026thinsp;=\u0026thinsp;0.01 (OR\u0026thinsp;=\u0026thinsp;5, 95% CI\u0026thinsp;=\u0026thinsp;2.578\u0026ndash;9.699). The mean intra-abdominal pressure was 11.46 in the case group and 9.2 in the control group. The study concluded that abdominal pain requiring surgical intervention is directly related to intra-abdominal pressure greater than 5 mmHg and related breathing rate (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). In our study, it was also found that a sudden increase in intra-abdominal pressure to 15 mmHg significantly increases postoperative pain in patients.\u003c/p\u003e \u003cp\u003eMario Schietroma et al. conducted a study to investigate the effect of intra-abdominal pressure on pain and the inflammatory process after adrenalectomy. The study included 51 patients who were randomly assigned to either the standard pressure group (12\u0026ndash;14 mmHg) or the low-pressure group (6\u0026ndash;8 mmHg) during pneumoperitoneum. Various markers of inflammation and pain were examined, including white blood cells, lymphocyte population, human leukocyte antigens, neutrophil elastase, interleukin levels, and C-reactive protein. The study found significantly higher concentrations of inflammatory markers in the standard pressure group compared to the low-pressure group. Additionally, there were significant changes in antigen expression on monocyte surfaces in the standard pressure group, indicating decreased antigen expression. In conclusion, reducing pneumoperitoneum pressure to 6\u0026ndash;8 mmHg during laparotomy resulted in reduced inflammatory response and postoperative pain in patients. (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Therefore, based on the findings of this study and our study, it can be inferred that the method, speed, and level of pressure have significant effects on different variables and biomarkers, leading to changes or stability in hemodynamics and postoperative pain.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur study revealed that the mean heart rate, blood pressure (systolic, diastolic, and mean arterial pressure), mean pain score, and administration of analgesics (pethidine) during recovery were significantly lower in the intervention group compared to the control group. However, there were no statistically significant differences in arterial blood oxygen saturation during surgery, duration of recovery between the two study groups. Therefore, for all patients requiring cholecystectomy, intra-abdominal pressure should be increased using the method obtained in our study (gradual insufflation) to achieve hemodynamic stability during surgery and reduce postoperative pain, leading to improved quality of care. Additionally, by reducing pain, patients experience less discomfort, reduced need for cardiac oxygen, and consequently lower risk of myocardial ischemia, decreased prolonged immobility, decreased suppression of the immune system, reduced risk of hyperglycemia, faster wound healing, reduced risk of atelectasis, and more.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics Approval and Consent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe studies involving human participants were reviewed and approved by Shahrekord\u0026nbsp;University of medical sciences (IR.SKUMS.REC.1400.117).\u0026nbsp;The patients/participants provided their written informed consent to participate in this study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgment\u003c/strong\u003e\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003eThe authors thank all the volunteers who participated in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003e\u0026nbsp;This research received no external funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe 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.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eKwon YJ, Ahn BK, Park HK, Lee KS, Lee KG. What is the optimal time for laparoscopic cholecystectomy in gallbladder empyema? Surgical endoscopy. 2013;27:3776-80.\u003c/li\u003e\n \u003cli\u003eTucker O, Fajnwaks P, Szomstein S, Rosenthal R. Is concomitant cholecystectomy necessary in obese patients undergoing laparoscopic gastric bypass surgery? Surgical endoscopy. 2008;22:2450-4.\u003c/li\u003e\n \u003cli\u003eLitwin DE, Cahan MA. Laparoscopic cholecystectomy. Surgical Clinics of North America. 2008;88(6):1295-313.\u003c/li\u003e\n \u003cli\u003eJoris JL, Noirot DP, Legrand MJ, Jacquet NJ, Lamy ML. Hemodynamic changes during laparoscopic cholecystectomy. Anesthesia \u0026amp; Analgesia. 1993;76(5):1067-71.\u003c/li\u003e\n \u003cli\u003eSanabria A, Dominguez LC, Valdivieso E, Gomez G. Antibiotic prophylaxis for patients undergoing elective laparoscopic cholecystectomy. Cochrane Database of Systematic Reviews. 2010(12).\u003c/li\u003e\n \u003cli\u003eSultan AM, El Nakeeb A, Elshehawy T, Elhemmaly M, Elhanafy E, Atef E. Risk factors for conversion during laparoscopic cholecystectomy: retrospective analysis of ten years\u0026apos; experience at a single tertiary referral centre. Digestive surgery. 2013;30(1):51-5.\u003c/li\u003e\n \u003cli\u003eYamazaki M, Yasuda H, Koda K. Single-incision laparoscopic cholecystectomy: a systematic review of methodology and outcomes. Surgery Today. 2015;45:537-48.\u003c/li\u003e\n \u003cli\u003eKhare A, Sharma SP, Deganwa ML, Sharma M, Gill N. Effects of dexmedetomidine on intraoperative hemodynamics and propofol requirement in patients undergoing laparoscopic cholecystectomy. Anesthesia, essays and researches. 2017;11(4):1040.\u003c/li\u003e\n \u003cli\u003eUmar A, Mehta KS, Mehta N. Evaluation of hemodynamic changes using different intra-abdominal pressures for laparoscopic cholecystectomy. Indian Journal of Surgery. 2013;75:284-9.\u003c/li\u003e\n \u003cli\u003eKorkmaz A, Alkış M, Hamamcı O, Besim H, Erverdi N. Hemodynamic changes during gaseous and gasless laparoscopic cholecystectomy. Surgery today. 2002;32:685-9.\u003c/li\u003e\n \u003cli\u003eSood J, Jayaraman L, Kumra VP, Chowbey PK. Laparoscopic approach to pheochromocytoma: is a lower intraabdominal pressure helpful? Anesthesia \u0026amp; Analgesia. 2006;102(2):637-41.\u003c/li\u003e\n \u003cli\u003eRishimani A, Gautam S. Hemodynamic and respiratory changes during laparoscopic cholecystectomy with high and reduced intraabdominal pressure. Surgical Laparoscopy Endoscopy \u0026amp; Percutaneous Techniques. 1996;6(3):201-4.\u003c/li\u003e\n \u003cli\u003eKim M-j, Kim T-S, Kim K-H, An C-H, Kim J-S. Safety and feasibility of needlescopic grasper-assisted single-incision laparoscopic cholecystectomy in patients with acute cholecystitis: comparison with three-port laparoscopic cholecystectomy. Journal of Laparoendoscopic \u0026amp; Advanced Surgical Techniques. 2014;24(8):523-7.\u003c/li\u003e\n \u003cli\u003eSato N, Shibao K, Mori Y, Higure A, Yamaguchi K. Postoperative complications following single-incision laparoscopic cholecystectomy: a retrospective analysis in 360 consecutive patients. Surgical endoscopy. 2015;29:708-13.\u003c/li\u003e\n \u003cli\u003eJategaonkar PA, Yadav SP. Prospective observational study of single-site multiport per-umbilical laparoscopic endosurgery versus conventional multiport laparoscopic cholecystectomy: critical appraisal of a unique umbilical approach. Minimally Invasive Surgery. 2014;2014.\u003c/li\u003e\n \u003cli\u003eRothman JP, Gunnarsson U, Bisgaard T. Abdominal binders may reduce pain and improve physical function after major abdominal surgery-a systematic review. database. 1966;2013.\u003c/li\u003e\n \u003cli\u003eCampos-Mu\u0026ntilde;oz MA, Villarreal-R\u0026iacute;os E, Chimal-Torres M, Pozas-Medina JA. Intra-abdominal pressure as a surgery predictor in patients with acute abdominal pain. Revista M\u0026eacute;dica del Instituto Mexicano del Seguro Social. 2016;54(3):280-5.\u003c/li\u003e\n \u003cli\u003eSchietroma M, Pessia B, Stifini D, Lancione L, Carlei F, Cecilia EM, et al. Effects of low and standard intra-abdominal pressure on systemic inflammation and immune response in laparoscopic adrenalectomy: a prospective randomised study. Journal of Minimal Access Surgery. 2016;12(2):109.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Intra-abdominal pressure, laparoscopic cholecystectomy, hemodynamics, pain","lastPublishedDoi":"10.21203/rs.3.rs-4601648/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4601648/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackgrounds\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGallbladder stones are a common health problem in developed countries, and the laparoscopic surgical method is widely used for treatment. It is important to identify surgical techniques that can reduce complications during and after surgery.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study included 100 patients, with 50 in the intervention group who underwent surgery with stepwise increased intra-abdominal pressure, and 50 in the control group who had surgery with 15 mmHg pressure. Demographic information was recorded, and hemodynamic changes during surgery and postoperative complications were documented. Data was compared using independent t-tests, ANOVA, and Chi-square tests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe results of our study showed that the intervention group had significantly more stable mean heart rate and blood pressure (systolic, diastolic, and mean arterial pressure) during surgery compared to the control group. The intervention group also had significantly lower frequency of nausea, mean pain, and administration of the analgesic Pethidine during recovery. However, there were no significant differences between the two study groups in mean arterial oxygen saturation during surgery, duration of hospital stay in recovery, frequency of vomiting, and headache.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBased on our findings, it is recommended to increase intra-abdominal pressure using the stepwise method employed in our study for all patients undergoing cholecystectomy. This can help achieve hemodynamic stability during surgery, reduce pain in patients, and improve the overall quality of treatment.\u003c/p\u003e","manuscriptTitle":"Evaluation of the effects of gradual increases in intra-abdominal pressure on blood pressure in a patient undergoing laparoscopic cholecystectomy.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-15 02:44:11","doi":"10.21203/rs.3.rs-4601648/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"dabcdaac-df48-4a4e-bd5e-957ab41165a2","owner":[],"postedDate":"July 15th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-07-22T12:47:03+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-15 02:44:11","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4601648","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4601648","identity":"rs-4601648","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}