Factors Influencing CRP levels in Laparoscopic and Robotic Total Hysterectomy

C-reactive protein (CRP) is a substance that responds to the acute phase of inflammation and is elevated postoperatively owing to surgical invasion, injury, or bleeding. 1 Patients with high postoperative CRP levels are at higher risk for complications such as intestinal injuries. 2 Postoperative CRP levels have also been reported to be useful in predicting postoperative complications of infection. 3 However, the significance of CRP levels measured using blood tests on the day after surgery in uncomplicated cases is not well understood. In this study, we aimed to determine which factors influence postoperative CRP levels in uncomplicated cases of gynecologic laparoscopic and robotic total hysterectomy.

In total, 180 patients were included in the study. Figure 1 presents a flow chart of patient selection. The patient with a postoperative abscess developed a fever from the third postoperative day and was diagnosed with a vaginal transection abscess by ultrasound and computed tomography. She was discharged on the 19th postoperative day after prolonged treatment with a vaginal transection drain and antibiotics. The median CRP level was 1.72 (IQR, 1.11–2.52) mg/dL, median age was 47.00 (IQR, 44.00–52.00) years, median BMI was 22.52 (IQR, 20.44–26.07) kg/m 2 , median blood loss was 50.00 (IQR, .00–111.75) mL, median operative time was 213.50 (IQR, 156.00–257.25) min, and median uterine weight was 179.00 (IQR, 109.75–260.00). The median preoperative hemoglobin was 13.50 (12.60–16.30) g/dL and the median postoperative hemoglobin decreased to 13.00 (12.00–14.90) g/dL. Forty-seven cases were included in the subgroup. The median increase from the preoperative CRP value was 2.35 (IQR, 1.14–3.3) ( Table 1 ). Flow diagram of patient selection. Characteristics of All Patients and Subgroups Abbreviations: BMI, body mass index; CRP, C-reactive protein. The P value of the multiple regression analysis was significant at less than .01. The adjusted R-squared value was .22. All the factors selected for this study (age, BMI, operative time, blood loss, and uterine weight) had variance inflation factors less than 2 and were not multicollinear. Among these factors, BMI and operative time were significantly associated with postoperative CRP levels: a 1-kg/m 2 increase in BMI was associated with an average increase in the CRP level of .231 mg/dL ( P value: .002, 95% confidence interval [CI]: .028–.119). A 1-min increase in operative time increased the CRP level by an average of .387 mg/dL ( P < .001, 95% CI: .0005–.010). Other factors (age, blood loss, uterine weight) were not found to be significant. Sensitivity analysis was a significant equation with a P value of .01 for multiple regression analysis; the adjusted R-squared value was .21. All the factors selected for this study (age, BMI, operative time, blood loss, and uterine weight) had variance inflation factors less than 2.5 and were not multicollinear. Among these factors, operative time was significantly associated with postoperative CRP levels. A 1-min increase in operative time was associated with an average increase in the CRP level of .477 mg/dL ( P value < .01, 95%: .004–.02) ( Table 2 ). Results of Multiple Regression Analysis Abbreviation: BMI, body mass index.

This study examined factors that may influence CRP levels the day after surgery in patients without complications. Patient factors included age and BMI, and operative factors included blood loss, operative time, and uterine weight. The results suggested that BMI and operative time may influence postoperative CRP levels. Further sensitivity analysis suggested that operative time may be a factor influencing the increase in CRP levels. Obese patients reportedly have mild inflammation, which contributes to elevated CRP levels. 9 Therefore, BMI may no longer be a significant factor when sensitivity analysis is performed only including cases with preoperative CRP levels above .01. Considering that the median BMI of the subgroup is higher than the overall median, it is possible that only prolonged operative time in obese patients leads to higher postoperative CRP levels. We did not find any previous reports examining the effect of prolonged operative time on postoperative CRP levels. Although not a gynecologic procedure, there was a report 10 of prolonged operative time in esophageal surgery being associated with a risk of postoperative complications. The study also suggested that longer operative time may lead to greater invasiveness than in cases with shorter operative time. Therefore, prolonged operative time may have led to an increase in postoperative CRP levels. This study is novel in that it included patients without postoperative complications. Some healthcare providers are concerned when postoperative blood tests show high CRP levels. However, considering the results of this study, the high CRP levels are thought to reflect BMI and operative time to some extent in those without postoperative infections. Therefore, when the postoperative CRP level is high, patients should be examined for infection, and if there is no evidence of infection, the patient should be followed up without any problems. There are some limitations to this study. The first is the small sample size. Second, our study only suggests an association between operative time, BMI, and postoperative CRP levels but does not demonstrate a causal relationship. Third, our study did not include medical history as a factor. Therefore, we performed a subgroup analysis using the increase from the preoperative CRP level as the outcome, allowing us to adjust for patient background. Fourth, this study did not include cases of malignancies. Surgeries for malignant tumors involve greater invasiveness, which may lead to different results from those of this study. Fifth, the CRP level is reported to peak at 48–72 h postoperatively. 11 In this study, the CRP level on the first postoperative day was used as the outcome measure, but if the CRP level on the second or third postoperative day was used instead, the results could have been different. Sixth, although the present study excluded patients who developed abscesses after surgery, it should be noted that CRP is a marker that is elevated in response to various types of acute inflammation; therefore, the possibility that unknown factors that were not examined in the present study could have affected the CRP level cannot be ruled out.

This study determined that in uncomplicated cases of laparoscopic and robotic total hysterectomy, operative time and patient BMI affected the postoperative CRP values. Future studies incorporating a larger sample size aimed at exploring the causal relationship of surgical time and BMI with the postoperative CRP level are warranted to validate these findings.

This was a single-center, retrospective cohort study conducted in a city hospital with 358 beds (28 for obstetrics and gynecology). The annual number of surgeries in the obstetrics and gynecology department is about 280. The study duration was from July 2016 to December 2022. Cases were registered using continuous sampling. Data were extracted from medical records. The study was approved by the Ethics Committee of the hospital (No. 23-011). Informed consent was obtained from all individuals included in this study. The data for this study was accessed between January 1, 2022, and April 30, 2023. Patients who underwent robotic or laparoscopic total hysterectomy for uterine fibroids, adenomyosis, or cervical neoplasia at our hospital were included. Patients who underwent laparotomy during surgery, developed an abscess after surgery, or were unable to have blood samples taken the day after surgery were excluded. There were no specific criteria for choosing between robotic and laparoscopic surgery, and each surgeon made a subjective decision. Patients underwent preoperative blood tests 3 months prior to surgery and the day before surgery. They were admitted to the hospital the day before surgery to ensure a good physical condition. In patients with massive bleeding, organ damage, or high degree of adhesion, which made it difficult to continue either robotic or laparoscopic total hysterectomy after initiation, laparotomy was performed. After the surgery was completed, the patients remained in the hospital until the next morning for observation. Blood tests, including the assessment of CRP levels, and a medical examination were performed the next morning to confirm that no complications had occurred. The patients were advised to start consuming solid food the day after surgery and were discharged after a wound check and a transvaginal ultrasound by a physician on the third to fifth day after surgery. In Japan, routine examinations are generally performed even for low-risk surgeries. 4 Also, hospital stays are long. 5 Therefore, such perioperative management is practiced in most Japanese facilities. The primary endpoint was the level of CRP (mg/dL) from the blood test performed on the morning of the day following surgery. The following factors were identified as possible factors that could affect the CRP level. First, age (years) 6 and body mass index (BMI) (kg/m 2 ) 7 were listed. In addition, as postoperative CRP values have been reported to be useful in quantifying tissue damage, 8 we chose operative time (min), blood loss (mL), and weight of the removed uterus (g) as indicators of tissue damage. Preoperative and postoperative hemoglobin levels were used as a reference for blood loss. The reliability of the data was ensured by multiple checks of the medical records by the authors. Patient characteristics were described using median and interquartile range (IQR) for continuous variables. Multiple regression analysis was used to examine factors affecting CRP levels. The sensitivity analysis in this study was performed using the change in preoperative and postoperative CRP levels as the outcome. All patients had blood tests performed between 3 months prior to surgery and the day before surgery; an increase from the preoperative CRP level cannot be accurately measured because a CRP level of less than .01 mg/dL would be unanalyzable. Therefore, a subgroup of patients with a CRP level greater than .01 mg/dL on the preoperative blood test was included in the study. As this was a small, single-center study and all cases within the relevant time period were included, the sample size based on effect estimation was not calculated. Statistical significance was set at a P value <.05. EZR (version 1.54) statistical software was used.