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Research Aricles

Quantification and influencing factors of perioperative hidden blood loss in patients undergoing laparoscopic ovarian cystectomy for benign ovarian tumours

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Abstract

This retrospective, monocentric study quantified hidden blood loss (HBL) and investigated its influencing factors in benign ovarian tumour patients undergoing laparoscopic ovarian cystectomy. Data from 153 patients who underwent laparoscopic ovarian cystectomy were retrospectively reviewed. HBL was calculated using the formula derived from ‘Nadler’ and ‘Cross’. Pearson correlation was carried out to measure the association between HBL and potential risk factors. The average HBL was 280.22 ± 168.42 mL, accounting for 84.13 ± 19.20% of total blood loss (TBL) (347.48 ± 179.05 mL), which was a change of almost fourteen-fold relative to median visible blood loss [20.00 mL (10.00 mL, 57.5 mL)]. Surgical time, number of excisional tumours and preoperative albumin values were risk factors for HBL. HBL represents a large proportion more than 80% of TBL in patients undergoing laparoscopic ovarian cystectomy. Collectively, HBL is helpful for estimating intraoperative blood loss and better guidance of haemostatic agents, which reduces postoperative complications and expedites postoperative recovery. Additionally, the estimation of HBL also contributes to the summary, reflection and improvement of surgical technique.

    IMPACT STATEMENT

  • What is already known on this subject? There has been a growing number of surgical patients with perioperative anaemia, which appears to be inconsistent with measured levels of visible intraoperative blood loss and postoperative drainage. This substantial but easily underestimated blood loss is known as hidden blood loss. To date, no published articles have evaluated HBL and its related risk factors in benign ovarian tumour patients undergoing laparoscopic ovarian cystectomy.

  • What the results of this study add? HBL accounts for a large amount of TBL in laparoscopy for benign ovarian tumours. Surgical time, number of excisional tumours and preoperative albumin values are risk factors for HBL.

  • What the implications are of these findings for clinical practice and/or further research? The management of HBL is important for the administration of perioperative blooding loss. In this context, HBL can be applied to estimate intraoperative blood loss and be better guidance of haemostatic agents to reduce postoperative complications and hasten postoperative rehabilitation. Additionally, the estimation of HBL also contributes to the summary, reflection and improvement of surgical technique.

Introduction

Benign ovarian tumours are some of the most common gynecological tumours worldwide and occur in women of any age, though they especially affect women of childbearing age. Benign ovarian tumours generally tend to have asymptomatic signs when the tumours in a small size. Unilateral or bilateral pelvic adnexal masses are mostly palpated through the gynecological examination or detected by the gynecological Doppler ultrasound. When the volume of benign ovarian tumours enlarges to a certain value and gradually occupies the pelvic and abdominal cavity, the patients might appear corresponding subjective symptoms such as abdominal distension, frequency of urination, constipation, and even mass can be directly touched in patients’ abdomen. The tumour may be either cystic or solid. One survey showed that the incidence of benign ovarian tumours was approximately 7% among 428 premenopausal women in Denmark (Christensen et al. Citation2002).

Compared with traditional laparotomy, laparoscopic ovarian cystectomy, an alternative clinical surgical procedure, is associated with smaller wounds, less intraoperative bleeding, lower complication rates and faster recovery (Buchweitz et al. Citation2005). Despite continuous improvements and reduced haemorrhage in perioperative management, there has been a growing number of surgical patients with perioperative anaemia, which appears to be inconsistent with measured levels of visible intraoperative blood loss (IBL) and postoperative drainage (Zhang et al. Citation2018).

This substantial but easily underestimated blood loss is known as hidden blood loss (HBL). Initially introduced by Sehat et al (Citation2000), the terminology HBL constituted approximately half of total blood loss (TBL) in total knee replacement. In subsequent years, many researchers focussed on the study of HBL in surgeries for multiple tumours, such as gastric cancer and cervical cancer. For example, the amount of HBL produced by laparoscopic gastrectomy was 322.2 ± 195.9 mL (64.3 ± 14.1% of TBL) in gastric cancer patients (Zhang et al. Citation2018). Currently, the mean HBL (345.2 ± 258.6 mL) in abdominal radical hysterectomy with bilateral pelvic lymph node dissection represented 38.3 ± 21.4% of TBL, while the HBL (185.1 ± 130.5 mL) could reach to 52.3 ± 28.1% of TBL in laparoscopy-assisted surgery (Zhao et al. Citation2019). These results suggested that HBL made up a large proportion of TBL and the successful management of perioperative HBL is of importance in accelerating postoperative recovery and significantly minimising the length of hospital stay.

Sustained excitement of sympathetic adrenal medulla system caused by the large amount of HBL led to the enhancement of cardiac contractility perioperatively, which placed an extra workload on the heart. Patients with underlying heart diseases, especially in elderly patients, could ultimately led to heart failure. Additionally, renal hypoperfusion due to the large amount of HBL might led to acute renal insufficiency and even renal necrosis (Wang et al. Citation2015). Perioperative HBL was totally much higher in amount than expectation while overlooked in clinical practice, which might accelerate the decline in haemoglobin (Hb), delay the healing of surgical incisions, greatly increase the risk of complications, extent the length of hospitalisation (Sehat et al. Citation2004; Miao et al. Citation2015). Such researches have documented that successful handling of perioperative HBL is of great significance for accelerating postoperative rehabilitation and shortening hospital stay.

Gender, the amount of albumin loss as well as patients with hypertension were proved to be related to the HBL in patients underwent laparoscopic gastrectomy (Zhang et al. Citation2018). Zhao et al. (Citation2019) believed that age, pathological types of tumour, preoperative value of Hb and haematocrit (Hct), surgical time and patients with diabetes were likely to increase the HBL of patients underwent radical hysterectomy with bilateral pelvic lymph node dissection perioperatively. To date, no published articles have evaluated HBL and its related risk factors in benign ovarian tumour patients undergoing laparoscopic ovarian cystectomy. Hence, in the present study, our investigation was carried out to quantify perioperative HBL and further explore its influencing factors in participants eligible for removal of benign ovarian lesions by using laparoscopic ovarian cystectomy with the aim of improving clinical practice regarding blood loss and hastening rehabilitation during the postoperative period.

Material and methods

Patients

Data on 153 patients who met the surgical indications for undergoing laparoscopic ovarian cystectomy in the Second Affiliated Hospital of Wenzhou Medical University by experienced surgeons titled with associate chief physician or above from May 1 2015, to May 1 2020, were retrospectively reviewed. The surgical indications were as follows: (1) the presence of a persistent ovarian tumour with at least 5 cm in diameter; (2) a recent and significant enlargement in size of the ovarian tumour; (3) ovarian tumour(s) with concomitant symptoms; (4) ovarian tumour(s) that appeared in a postmenopausal woman. In addition, the inclusion criteria for patients were as follows: (1) a confirmed pathological diagnosis of a benign ovarian tumour including ovarian serous tumour, mucous tumour, teratoma and so on; (2) general anaesthesia during the operation; (3) laparoscopic ovarian cystectomy as the procedure. The general exclusion criteria for patients were as follows: (1) combined with other gynecological disorders; (2) pregnant or lactating women; (3) patients with perioperative blood transfusion; (4) a history of taking drugs that can affect perioperative blood coagulation; (5) a history of hematological disorders; (6) a history of gastrointestinal bleeding; (7) a history of cardiovascular or cerebrovascular diseases; (8) a history of immunological or endocrine system diseases; (9) a history of major surgery within 30 days; (10) disorders of liver or renal function; or (11) a need for more than 2000 mL of intravenous rehydration perioperatively.

The protocol of this research was reviewed and approved beforehand by the Ethics Committee of the Second Affiliated Hospital of Wenzhou Medical University (No. L-2020-29). Written informed consent was provided by all enrolled subjects or their relatives prior to participation.

Surgical procedures

A comprehensive assessment of the patients’ general condition was performed prior the operation in conjunction with anaesthesiologists. All Patients were informed of the purpose, methods, the potential complications of laparoscopic ovarian cystectomy in details before surgery, and signed written informed consents. Patients routinely prohibited of drinking and fasting for 6–8 h and urinary catheterisation was executed preoperatively. The specific surgical procedures were as follows: (1) After general anaesthesia, patients were placed in the supine position with the operating table rotated 30° into the Trendelenburg position. (2) Followed by conventional disinfection and spreading towels, a 10-mm trocar was inserted through the umbilicus into abdominal cavity. The CO2 pneumoperitoneum was then established to maintain the intraabdominal pressure at approximately 15 mmHg. (3) A 30° laparoscope was performed to explore the pelvic cavity via the umbilical port, the rest of trocars were inserted under laparoscopic guidance. (4) A small incision was then made along the ovarian cortex by using scissors after the ovaries were fully exposed, the entirely ovarian tumour was isolated from the ovarian cortex by blunt dissection. (5) The rest ovarian cortex was routinely sewed back with a running suture of 2/0 for complete hemostasis. If necessary, bipolar electrocoagulation was applied for hemostasis. (6) The resected specimens were removed through periumbilical incision with a specimen bag and then sent for routine intraoperative rapid frozen pathologic examination and postoperative pathologic examination. (7) After thorough pelvic cavity lavage and confirming no active bleeding, an indwelling drainage tube was placed towards the end of the operation. (8) Finally, the CO2 gas was deflated, all the cannulas were completely removed and the skin incisions were sutured.

All the patients we have collected were not treated with topical haemostatic agents or prophylactically used of tranexamic acid during the perioperative protocol.

Data collection

Surgical duration and intraoperative visible blood loss (VBL) were monitored carefully by an experienced anaesthetist and recorded in the anaesthesia records. Intraoperative VBL was measured based on the sum of total amount of blood in the aspirator (excluding lavage fluid) and the weight of gauze soaked with blood at the completion of surgery after subtracting the dry weight of the gauze. The fluid level in the drainage bag until removal of the drainage tube after surgery was recorded as postoperative blood loss (PBL). The volume of intraoperative blood loss during the operation plus total drainage of post-operation was calculated as VBL. The patients’ demographic variables, including age, height, weight, body mass index (BMI) and previous medical history, were recorded by the physicians in charge using the electronic medical records of our hospital. BMI was computed according to the following equation: BMI = weight (kg)/[height (m)]2. The complete blood cell count was measured before surgery and on postoperative day 2 or 3 when the systemic hemodynamics had reached a stable status (Wen et al. Citation2018). The number of ovarian tumours removed during the operation (1 or ≥2) and the size of each tumour were recorded by the surgeon in operative document. In cases of multiple tumours, the size of the largest mass was considered representative of the sizes of the ovarian tumours in our study. The preoperative plasma albumin level, Hb and Hct, together with the second- or third-postoperative-day Hb and Hct were also obtained from the electronic medical records.

Calculation of HBL and related variables

Each individual patient’s estimated blood volume (EBV) was computed by taking into account the patient’s height and weight using the formula derived from Nadler et al. (Citation1962), as follows: EBV(L)=0.3561×height(m)3+0.03308×weight(kg)+0.1833.

TBL was calculated using the equation described by Gross (Citation1983) as follows: TBL(L)=EBV(L)×(HctpreHctpost)/Hctave. where Hctpre represents the initial preoperative Hct, Hctpost is the Hct from the second or third postoperative day, and Hctave is the mean value of Hctpre and Hctpost.

Eventually, the HBL required for this research was calculated based on Sehat’s formula (Sehat et al. Citation2004):

HBL = TBL − intraoperative VBL − postoperative VBL

Additionally, the volume (cm3) of the largest ovarian tumour was calculated using the formula of the prolate ellipsoid as follows (Abbas et al. Citation2015): volume=π×a×b×c/6 where a, b and c (cm) represent the length, width and height, respectively, of the ovarian tumour according to the intraoperative findings.

Statistical analysis

The analysis of risk factors influencing HBL was identified by using Pearson correlation, including two qualitative variables (the number of tumours, the volume of the largest tumour) and four quantitative variables (age, BMI, surgical time, preoperative Hb values). For the qualitative variables, the number of tumours was classified as single or multiple (≥2). A single tumour was set to ‘0’, and multiple tumours were set to ‘1’. A value of ‘0’ was assigned if the maximum volume of resected tumour was < median tumour volume and ‘1’ if the volume was ≥ median tumour volume. Descriptive statistics are presented as frequencies (percentages), medians (P25, P75) or means ± standard deviations (SDs). All statistical analyses were carried out using IBM SPSS Statistics software application version 22.0, values of p < 0.05 were considered to indicate a statistically significant difference.

Results

Baseline information and demographic characteristics of the patients

A total of 153 patients undergoing laparoscopic ovarian cystectomy were initially admitted to this study. All patient’s demographic information and basic characteristics are presented in . The average age of the cases was 28.28 ± 6.82 years (9–48 years), and the mean baseline BMI was 22.07 ± 3.32 kg/m2 (16.21–33.30 kg/m2).

Table 1. Baseline information, general characteristics and benign ovarian tumour characters of the patients.

Benign ovarian tumour characteristics of the patients

Regarding the number of excisional tumours as in , 132 cases (86.3%) had a single tumour, and 21 cases (13.7%) had multiple tumours. The median volume of the largest excisional tumour was 65.38 cm3 with an interquartile range of 112.91 cm3 (18.83 cm3, 131.80 cm3).

Perioperative clinical data of the patients

As shown in , the preoperative plasma albumin values were relatively normal (normal range: 40–55 g/L) for all cases, with the mean level of 45.08 ± 2.84 g/L. Six of the patients (3.92%) had anaemia (<110 g/L) before surgery, and eighteen of the patients (11.76%) had detectable postoperative anaemia. Among postoperative patients, 17 cases had mild anaemia (<110 g/L and ≥90 g/L) and 1 cases had moderate anaemia (<90 g/L and ≥60 g/L). The mean haemoglobin level in 153 patients before surgery was 132.20 ± 10.13 g/L, which was within the normal range, while the mean postoperative haemoglobin level was 119.48 ± 9.67 g/L. Overall, the relative drop in mean haemoglobin was 12.73 ± 6.77 g/L. The average operative time was 77.42 ± 32.20 min, and the duration of postoperative hospitalisation for patients undergoing laparoscopic ovarian cystectomy was 3.21 ± 0.92 days.

Table 2. Perioperative clinical data of the patients.

The average preoperative Hct baseline value and the Hct on postoperative day 2 or 3 were 0.40 ± 0.03 and 0.36 ± 0.03, respectively. The median VBL was 20.00 mL (10.00 mL, 57.50 mL), and the average HBL was 280.22 ± 168.42 mL, accounting for 84.13 ± 19.20% of TBL (347.48 ± 179.05 mL).

Potential risk factors for HBL

Pearson correlation was carried out to assess the association between HBL and potential risk factors. The results were summarised in , the volume of the largest excisional tumour, age and BMI exhibited no significant association with HBL (p > 0.05). However, surgical time, number of excisional tumours and preoperative albumin values were positively correlated with HBL (p = 0.028, p = 0.024, p = 0.000, respectively).

Table 3. Pearson correlation analysis for an analysis for potential risk factors for HBL.

Discussion

Since the proposal of HBL was proposed by Sehat et al. in 2000, HBL has been considered a significant factor in orthopaedic surgery. Nevertheless, the application of HBL to gynecological procedures has been limited. Zhao et al. (Citation2019) revealed that HBL made up a significant percentage of TBL in stage IA-IIA cervical carcinoma treated with radical hysterectomy and pelvic lymphadenectomy by laparotomy or laparoscopy. Additionally, they observed that the amount of HBL in patients undergoing laparotomy was larger than that in patients undergoing laparoscopy. The generally accepted mechanism was that 40% of HBL was caused by a haemolytic reaction following subsequent reperfusion and that up to 60% of it was caused by residual blood extravasated into tissue (Sehat et al. Citation2000). Furthermore, the production of various inflammatory mediators and the secretion of vasoactive substances led to the dilatation of capillaries, then leading to the increase of the permeability of blood vessel wall and the promotion of a large amount of perioperative bleeding into tissue space (Erskine et al. Citation1981). Additionally, a potential explanation for HBL was that the releasing free fatty acids produced by fat emboli in the general blood circulation damaged red blood cells and haemoglobin membrane molecules through lipid peroxidation, resulting in HBL (Bao et al. Citation2013). Antioxidants could significantly reduce the volume of HBL by protecting the erythrocyte from oxidation, suggesting the erythrocyte peroxidation might be also involved in the formation of HBL (Bao et al. Citation2013).

Nevertheless, the application of HBL to gynecological procedures has been limited. Due to the use of the Trendelenburg position during gynaecologic procedures, the measurement of VBL always leads to an artificial underestimation of blood loss due to blood accumulation in the abdominal cavity, which leads to overestimation of HBL perioperatively. In our research, the VBL [20.00 mL (10.00, 57.5)] was far lower than the TBL (347.48 ± 179.05 mL) assessed in patients treated with laparoscopic ovarian cystectomy. Surprisingly, the average HBL (280.22 ± 168.42 mL) accounted for 84.13 ± 19.20% of the TBL, which was an almost fourteen-fold change relative to VBL.

Moreover, 12 patients suffering from secondary anaemia had normal preoperative Hb levels. The relative median decrease in Hb (12.73 ± 6.77 g/L) was inconsistent with the intraoperative and postoperative VBL, implying that unidentified blood loss would be dangerous to many patients and would probably result in severe anaemia. This result was similar to that in Wu’s study (Wu et al. Citation2017), where the actual amount of bleeding was much higher than the VBL in patients undergoing percutaneous kyphoplasty surgery. HBL might be correlated with enhanced risk of postoperative anaemia, which is likely to prolong the length of hospitalisation, affect overall mortality and lead to readmission (Jiamset and Hanprasertpong Citation2016; Zhao et al. Citation2019). Excessive blood loss and blood transfusion might occur secondary severe complications and seriously affect the prognosis of patients, especially patients with preoperative comorbidities. Paying more attention to HBL would accelerate postoperative recovery and avoid the adverse effects of anaemia.

More importantly, Pearson correlation analysis revealed multiple relational factors including surgical time, number of excisional tumours and preoperative albumin values were risk agents for HBL. However, age, BMI, and the volume of the largest excisional tumour had no significant influence on HBL.

For example, Miao et al. (Citation2015) detected that the volume of HBL was significantly correlated with age in total hip arthroplasty. In the study by Zhang et al. (Citation2018), patients undergoing laparoscopic gastrectomy who were over 70 years old had much more HBL and a longer postoperative hospital length of stay than patients under 70 years old. Furthermore, Zhao et al. (Citation2019) observed a larger amount of HBL in elderly patients because of their fertility history and relaxation effects induced by senescence in fibrous tissues of uterus. Our statistics suggested that patient’s age (mean of 28.39 ± 7.10 years) was an unrelated factor affecting HBL in patients undergoing laparoscopic ovarian cystectomy. It was speculated that the cases collected in our study were mostly women in childbearing age with a small age distribution range and with stronger ability for self-compensation in terms of perioperative hemodynamics.

Moreover, one study demonstrated that obesity based on a BMI exceeding 30 kg/m2 could increase the amount of bleeding in patients undergoing abdominal myomectomy (Çinar et al. Citation2016). Lower central and peripheral venous pressure would lead to less blood loss under general anaesthesia. However, obesity increases ventilation pressure with a reduction in chest wall and total respiratory system compliance, which contributes to the elevation of venous pressure and promotes blood loss through vascular permeability16. In contrast, Prasad et al. (Citation2007) found that BMI has no relationship with HBL in total knee arthroplasty. Consistent with this conclusion, our study also showed that BMI is not an influential factor for HBL in benign ovarian tumour patients undergoing laparoscopic ovarian cystectomy. Due to the small proportion of obese patients in this research where only five patients in our research had a BMI over 30 kg/m2, with a maximum value of 33.30 kg/m2 and that the incidence of benign ovarian tumours trended towards younger women who always have better weight control, little impact of BMI on HBL. To obtain a more reliable correlation between BMI and HBL, more cases of obese patients should be included in future studies.

Considering the influence of tumour size on HBL, Sleiman et al. (Citation2020) calculated that myoma diameter was a predictor of the amount of blood lost, with an increase of 2.51 ml of blood lost and 0.292 drop in haemoglobin unit for every 1 mm increase in myoma size. While Ye et al. (Citation2020) demonstrated that the volume of the largest excisional tumour was not a major risk factor for HBL in myomectomy. In addition, no statistically significant difference was found in estimated blood loss according to the size of benign ovarian tumour by laparoscopy (Lim et al. Citation2012). Meanwhile, our results also showed that the size of the removed tumour was not a significant predictor of HBL in benign ovarian tumour patients undergoing laparoscopic ovarian cystectomy. Therefore, the correlation between HBL and the size of benign ovarian tumour remained controversial and larger study cases need to be enrolled to validate it in further studies.

Cao et al. (Citation2018) proved that the longer operative time was closely related to a greater amount of HBL in percutaneous kyphoplasty. Ju and Hart (Citation2016) demonstrated that the extension of surgical time led to increased HBL in anterior lumbar interbody fusion. These results were in agreement with the finding of our study, which showed that as the length of surgical time increased, the overall amount of HBL became higher. We thus speculated that with the extension of operation time, more blood infiltrated into the tissue and sequestered into the third space including the peritoneal cavity and intestinal space, leading to the decrease of VBL and increase of the amount of HBL.

Notably, Ye et al. (Citation2020) proved that the number of uterine fibroids removed during the laparoscopic myomectomy was a predictor of HBL perioperatively. Similarly, the number of excisional tumours was a potential risk factor for HBL in laparoscopic ovarian cystectomy in our study. Perhaps resection of these multiple tumours increased the overall area of surgical bleeding, in turn leading to increased blood constituent extravasation. Consequently, the number of excisional tumours was shown to be an independent predictor of HBL in benign ovarian tumour patients.

Hypoalbuminemia is often attributed to the alteration of protein catabolism, along with surgery and perioperative protein deficiency. Common postoperative complications of hypoalbuminemia include wound infection, wound dehiscence, delayed wound healing, longer hospitalisation times and increased mortality. Hypoalbuminemia was found to be positively related to HBL in patients undergoing laparoscopy-assisted gastrectomy (Zhang et al. Citation2018). Consistently, Zhao et al. (Citation2019) revealed that preoperative albumin values positively correlated with the amount of HBL in radical hysterectomy and pelvic lymphadenectomy, which was similar to our findings in that the preoperative albumin value was a significant risk factor for HBL in laparoscopic ovarian cystectomy. High preoperative albumin values might participate in the activity of hyperfibrinolysis, which causes the abnormal absorption of HBL in the third space (Liu et al. Citation2011).

Nevertheless, this research has several limitations to consider. First, only a relatively fewer participant cases were retrospectively included due to the screening rules for patient inclusion in this single-center study, and larger numbers of benign ovarian tumour samples in prospective multicenter studies is required to assess the generalisability of our preliminary findings. Additionally, benign ovarian tumour samples with perioperative blood transfusion or using anticoagulant also should be included to investigate the HBL. Thirdly, it was assumed that the blood volume remained in a stable state perioperatively and that the body fluid completed its transfer and reached hemodynamic stability on postoperative day 2 or 3. This situation might change under nonideal conditions, directly leading to an inaccurate estimation of HBL. Furthermore, the tissue fluid, as a component of the drainage liquid, was deemed as VBL during the perioperative period, which might lead to a slight underestimation of HBL. Lastly, individual surgical performance may also have effect on the assessment of HBL. However, in our study all the surgeons were experienced who titled with associate chief physician or above, which might affected HBL evaluation to some extent.

Conclusion

Overall, HBL accounts for a large amount of TBL in laparoscopy for benign ovarian tumours. Surgical time, number of excisional tumours and preoperative albumin values are risk factors for HBL. The management of HBL is important for the administration of perioperative blooding loss. In this context, an accurate evaluation of HBL is helpful for estimating intraoperative blood loss and better guidance of haemostatic agents as soon as possible to reduce postoperative complications and hasten postoperative rehabilitation. Additionally, the estimation of HBL also contributes to the summary, reflection and improvement of surgical technique.

Acknowledgements

We are grateful to all patients and physicians who have made contributions to the completion of this research. We especially wish to acknowledge the generous support of the Gynecology and Obstetrics Integrated Chinese and Western Medicine of Zhejiang Province fund (No. 2017-XK-A42).

Disclosure statement

The authors stated that there are no conflict of interests related to this article.

Data availability statement

The datasets generated and analysed in the present study are available from the corresponding author on reasonable request.

Additional information

Funding

This work was financially supported by the Gynaecology and Obstetrics Integrated Chinese and Western Medicine of Zhejiang Province [No. 2017-XK-A42].

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