Open Journal Systems

ORIGINAL CONTRIBUTIONS

Received: December 22^nd 2014

Accepted: March 4^th 2015

Waist-hip ratio and perioperative bleeding in patients who underwent radical prostatectomy

Víctor León-Ramírez,^a Janaí Santiago-López,^b Juan Gabriel Reyes-Rivera,^c Edgar Miguel-Soto^c

^aHospital de Cardiología, Centro Médico Nacional Siglo XXI

^bHospital de Especialidades, Centro Médico Nacional Siglo XXI

^cServicio de Anestesiología, Departamento de Cirugía, Hospital de Especialidades, Centro Médico Nacional La Raza

Instituto Mexicano del Seguro Social, Ciudad de México, México

Communication with: Víctor León-Ramírez

Telephone: (55) 5627 6900, extension 22181

Email: viler15@hotmail.com

Background: Radical prostatectomy is associated with perioperative bleeding and multiple transfusions. Abdominal obesity is a perioperative risk factor. We suggest that the adipocytes have a protective effect in oncological patients undergoing radical prostatectomy. The aim was to evaluate the effect of waist-hip ratio (WHR) on the amount of bleeding and perioperative transfusion requirements in oncological patients undergoing radical prostatectomy.

Methods: We performed a cohort study in 156 patients. We had two groups: the control group (WHR < 0.95) and the problem group (WHR ≥ 0.95). Blood loss and fractions transfused during surgery and in the postoperative period were recorded. In the analysis of variables, for descriptive statistics we used measures of central tendency and dispersion. Inferential statistics was obtained by chi square, Student’s t test, Mann-Whitney U and ANOVA. A p < 0.05 was significant.

Results: We found significant differences in weight, body mass index, waist, WHR, perioperative bleeding, fractions transfused, permanence of the catheter, and hospital days.

Conclusion: Patients who underwent radical prostatectomy with a WHR ≥ 0.95 had a magnitude of perioperative bleeding and transfusion requirements with a WHR < 0.95.

Keywords: Waist-hip ratio; Prostatectomy; Bleeding; Abdominal obesity

Radical prostatectomy (RP) is the gold standard treatment for symptomatic prostatic obstruction of the lower urinary tract, but it is traditionally associated with perioperative bleeding and a high transfusion rate. Bleeding during and after surgery has an incidence of 2.5% and can lead to significant morbidity and mortality.^1-4

Perioperative bleeding has been attributed to local and systemic fibrinolysis generated by the release of urokinase from the urinary tract during the surgical procedure and the release of tissue plasminogen activator (t-PA) by manipulation of the prostate tissue (both released locally and, subsequently, to the bloodstream).^5-8 Fibrinolysis is diagnosed by titration in the peripheral blood of products of fibrin degradation, such as dimer D.⁹ Other coagulation disorders have also been identified, such as thrombocytopenia, hypofibrinogenemia, and prolongation of prothrombin time.^10,11

To characterize the intraoperative blood loss and transfusion requirements in patients undergoing RP, independent predictive risk factors have been determined, including prostate size, smoking, creatinine levels, surgical anesthetic time, overweight, and obesity.¹² It is generally accepted that comorbid conditions, such as obesity, represent an important perioperative risk factor; however, some studies previously published in the literature suggest a possible protective effect of adipocyte in patients at risk of bleeding. Although this association has been little studied and the results show a marked heterogeneity, a possible inverse relationship has been noted between body mass index (BMI) and perioperative bleeding.¹³

Based on this, we plan to analyze the effect of waist-hip ratio (WHR) on the amount of perioperative bleeding and transfusion requirements in patients undergoing RP. In developing our study we considered that the definition of obesity according to BMI has some limitations from a clinical point of view. While it has been agreed that obesity should be defined in terms of BMI and values over 30 kg (m2)-1 have been taken to define it, there is the notion that obesity is determined depending on the location of excess fat, not the excess of weight, which supports the premise that a high proportion of abdominal fat better defines the concept and therefore the anthropometric variable that best evaluates it is the relationship between waist and hip circumferences (WHR).¹⁴

There is evidence to show that patients with an expansion of abdominal fat, especially visceral adipose tissue, develop a low-level chronic inflammatory process, which is characterized by endothelial dysfunction, hypercoagulability, hypofibrinolysis, and platelet activation.

The disorders associated with endothelial dysfunction resulting from the expansion of abdominal fat include the expression of adhesion molecules; decreased synthesis of nitric oxide (NO) and prostacyclin (PGI2); decreased sensitivity of vascular smooth muscle to vasodilators of endothelial origin; increased release of endoperoxides and production of reactive oxygen species (ROS); increased secretion of endothelin-1 (ET-1) and serum concentration of the soluble form of the cell adhesion molecule vascular-1 (sVCAM-1), among others, which is encouraged by some adipokines, such as interleukin-1 (IL-1), interferon-gamma (IFN-gamma), E-selectin interleukin-1beta (IL-1beta), and tumor necrosis factor alpha (TNF-alpha).

As regards coagulation, high levels of fibrinogen, three dependent vitamin K factors (VII, IX, and X), factor XIII, and von Willebrand factor have been found. Hyperfibrinogenemia is explained mainly because the adipokines interleukin-6 (IL-6) and TNF-alpha induce the synthesis of acute phase proteins such as fibrinogen and C-reactive protein (CRP) in the liver. Changes in the fibrinolytic system are mainly characterized by an increased synthesis of plasminogen activator inhibitor 1 (PAI-1), by adipocytes and platelets. As regards platelet hyperactivity, initially resting platelets bind to damaged endothelium through P-selectin molecules (PSGL-1 [P-selectin glycoprotein ligand-1]), generating conformational changes by GPIb / VWF binding and subsequently via integrins (GPIIb-IIIa / ICAM-1 or aV-beta-3). Thus, platelets are activated. OxLDL may contribute to activation, since these exhibit OxLDL receptors (CD36 and LOX-1). Once activated, they secrete multiple molecules, among which we can mention: IL-1 and CD40L, MCP-1 (monocyte chemoatractant protein); PF4, CXCR3, cytokines, RANTES (CCL5), PDGF (platelet-derived growth factor), ENA-78 (epithelial neutrophil activating peptide-78), CXCL5, platelet agonists (ADP, TxA2), and serotonin, among others. This increased response of platelets decreases the fluidity of their membrane due to changes in their lipid composition, which causes increased arachidonic acid metabolism with increased production of platelet agonists and increased intracellular free calcium. This promotes platelet aggregation. Moreover, serum levels of adiponectin and leptin are increased, which further promotes endothelial activation and assists in the recruitment of other platelets.

While from the pathophysiological point of view these variations are considered a surgical risk factor, by promoting a prothrombotic state, they can reach clinical significance in some patients who are scheduled for surgery who are at high risk of bleeding.

Thus, we hold that adipose tissue is a complex secretory and endocrine organ that can contribute beneficially to counteract the deleterious effects of fibrinolysis, minimizing post-surgical bleeding and reducing transfusion requirements in the perioperative period of patients undergoing radical prostatectomy.^15-17

Methods

With the approval of the Hospital Commission for Scientific Research, a group of 156 patients of the institution were included in a prospective, longitudinal, and open cohort study, to assess the effect of waist-hip ratio on the amount of perioperative bleeding and transfusion requirements in cancer patients undergoing radical prostatectomy. The study included patients scheduled for elective surgery, who had normal preoperative coagulograms, no history of congenital or acquired blood dyscrasia, surgical anesthetic risk according to the ASA I-IV, and who agreed to participate. It excluded those who refused transfusion, with serum creatinine greater than 2.0 mg/dL, who had a history of heavy smoking (tobacco use index > 30), and those who took oral anticoagulants or antiplatelet drugs in the 10 days prior to the surgical event . During the preoperative evaluation, anthropometric variables of patients, such as weight, height, waist circumference, and hip circumference were measured, and patients with a waist-hip ratio < 0.95 were identified, who constituted the control group; those with a waist-hip ratio ≥ 0.95 constituted the problem group. In cases where the patient had prior medication, they continued to take it, except for drugs involved in coagulation; if the patient had glycoprotein IIb / IIIa inhibitor or heparin infusion drugs, these were suspended six hours prior to the surgery.

Upon arrival in the operating room, all patients had their noninvasive blood pressure (NIBP) and heart rate (HR) monitored, had continuous electrocardiography (EKG) done, and oxygen saturation (SpO2) measured with multiparameter equipment. They had nasal cannula placed for supplementary oxygen at a flow of 2 L / min. The anesthetic technique was considered by the attending anesthesiologist, in addition to initiating an infusion of crystalloid at 7 mL / kg / hr. The cannulation of the radial artery and high flow peripheral venous access were then done, after local infiltration and coagulogram monitoring, specifically, prothrombin time (PT), partial thromboplastin time (PTT), international normalized ratio (INR), and blood count (hemoglobin [Hb], hematocrit [Ht], platelets), using the ABL 5 Radiometer RCopenhagen and ACL TOP IL devices, respectively. During the anesthetic, artery line samples were taken at intervals of one hour to guide transfusion therapy. The collected samples were sent immediately to the central laboratory for processing. The hemoglobin limit for the administration of erythrocyte concentrate was 9 mg/dL, in any case considering the particular situation of each patient.  

Variables were recorded at four different times: T0: baseline values, upon arrival in the operating room before starting the surgery; T1: upon arrival in the post-anesthesia intensive care unit (PACU); T2: twenty-four hours after finishing surgery, and T3: when removing drainage.

The results were recorded on the data collection sheet, plus the following data: total anesthesia time, operative time, blood loss, bleeding, and fractions that were transfused from their arrival in the operating room until the removal of drainage (perioperative).

Descriptive statistics were used, using measures of central tendency and dispersion. For quantitative variables with normal distribution, arithmetic mean and standard deviation were obtained; and for nominal qualitative variables, ratio rates and proportions. Inferential statistics was applied with Chi-squared test in the case of qualitative variables, Student’s t-test for quantitative parametrics, and Mann-Whitney’s U for nonparametric variables. To complement the content analysis, an analysis of variance (ANOVA) was made. This showed any possible differences in the average amount of bleeding as a function of time. In all cases a value of p < 0.05 was considered statistically significant. The information was processed with SPSS software, version 22.0.

Results

163 patients who underwent radical prostatectomy in the period from February 2011 to October 2014 were included in the study; five were excluded from the analysis due to reoperation due to bleeding secondary to deficiencies in surgical technique, and two more due to transfusion reaction, so there was a total of 156 patients. As for preoperative variables, the average age was 64.1 years with a range of 47 to 78 years of age and standard deviation (SD) of 6.58. The average weight was 73.84 kg, ranging from 59 to 109 kg, and SD was 14.93. The average height was 1.63 m with a range from 1.52 to 1.89 m and SD was 0.12. The body mass index (BMI) was 27.45 kg/m² with a range from 21.18 to 36.84 kg/m² and SD was 3.53. The average waist circumference was 99.42 cm with a range from 82.5 to 117.7 cm and SD was 6.3. The average hip circumference was 103 cm with a range from 94 to 110 cm and SD was 4.1. The average waist-hip ratio (WHR) was 0.96 with a range from 0.87 to 1.19 and SD was 0.08. 66.03% of patients had an ASA physical status of III. 100% had a diagnosis of prostate carcinoma. 88.46% of patients had associated comorbidities, of which 55.76% had multiple. Hypertension was evidenced in 61.6% of patients, diabetes mellitus 2 in 59.2%, dyslipidemia in 17.2%, and history of acute myocardial infarction in 9.2%. The average value of preoperative prostate-specific antigen (PSA) was 10.1 ng / mL-1, with a range from 3.9 to 23.1 ng / mL and SD of 4.8 ng / mL. Preoperative values ​​of transrectal prostate biopsies were analyzed by the Gleason grading system; well-differentiated tumors (Gleason 2-4) were found in 41 patients (26.28%), moderately differentiated (Gleason 5-7) in 91 (58.33%), and poorly differentiated (Gleason 8-10) in 24 patients (15.39%). The two groups were comparable in terms of age, height, hip circumference, physical status (ASA), PSA figures, and Gleason biopsy stage. However, we found significant differences in weight, BMI, waist circumference, and WHR (Table I).