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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 14  |  Issue : 8  |  Page : 173-179

Clinical research of goal-directed fluid therapy in elderly patients with radical resection of bladder cancer


1 Department of Anesthesia, The Affiliated Hospital of North China University of Science and Technology, Tangshan 063000, Hebei, P.R. China
2 Department of Urology Surgery, The Affiliated Hospital of North China University of Science and Technology, Tangshan 063000, Hebei, P.R. China
3 Department of Critical Care Medicine, The Affiliated Hospital of North China University of Science and Technology, Tangshan 063000, Hebei, P.R. China
4 Department of Respiratory Medicine, The Affiliated Hospital of North China University of Science and Technology, Tangshan 063000, Hebei, P.R. China

Date of Web Publication26-Mar-2018

Correspondence Address:
Shu-Bo Zhang
Department of Anesthesia, The Affiliated Hospital of North China University of Science and Technology, No. 73, South of Jianshe Road, Lubei District, Tangshan 063000, Hebei
P.R. China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.183206

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 > Abstract 


Objective: The aim of this study is to investigate the clinical effect of goal-directed fluid therapy in elderly patients with radical resection of bladder cancer.
Materials and Methods: Seventy-six elderly patients with radical resection of bladder cancer were selected from October 2012 to October 2014 and randomly divided into two groups, in which 38 patients received routine treatment as the control group and 38 patients received goal-directed fluid therapy based on routine treatment as the observation group. The treatment effect was compared between two groups.
Results: The cardiac index, stroke volume variability, mean arterial pressure, central venous pressure, central venous oxygen saturation, oxygen supply index, oxygen consumption index, and oxygen uptake rate in observation group were distinctly higher than those in control group at T1, T2, T3, and T4 while the artery serum lactate and S100-β were apparently lower than those in control group at T1, T2, T3, and T4. The urine volume and colloidal infusion were obviously elevated when compared with those in control group at T1, T2, T3, and T4 while the crystalloid infusion volume, total liquid infusion volume, hospitalization time, and expenses were significantly less than those in control group; further, similar tendency was also found regarding the complication incidences of nausea, vomiting, or hypotension in observation group. The postoperative flatus and postoperative food-taking times were visibly earlier than those in control group (both P < 0.05).
Conclusion: The goal-directed fluid therapy is beneficial for stabilization of hemodynamic status and maintenance of oxygen balance of supply and demand, and it is worthy of clinical expansion for good microcirculation perfusion, reduction in therapeutic time and expenses of patients, and less complications and superior security.

Keywords: Clinical effect, goal-directed fluid, radical resection of bladder cancer, the elderly


How to cite this article:
Liu TJ, Zhang JC, Gao XZ, Tan ZB, Wang JJ, Zhang PP, Cheng AB, Zhang SB. Clinical research of goal-directed fluid therapy in elderly patients with radical resection of bladder cancer. J Can Res Ther 2018;14, Suppl S1:173-9

How to cite this URL:
Liu TJ, Zhang JC, Gao XZ, Tan ZB, Wang JJ, Zhang PP, Cheng AB, Zhang SB. Clinical research of goal-directed fluid therapy in elderly patients with radical resection of bladder cancer. J Can Res Ther [serial online] 2018 [cited 2019 Jun 19];14:173-9. Available from: http://www.cancerjournal.net/text.asp?2018/14/8/173/183206




 > Introduction Top


As a common clinical, urological disease, bladder cancer runs in the first place of morbidity in all malignant tumors of the urinary system.[1] In recent years, the morbidity of bladder cancer increases significantly with the rising of the aging population and the weakening of physical function, which becomes a serious impact on the health of the elderly who are among the high-risk population of bladder cancer.[2] Surgeries are effective treatments for bladder cancer, of which the commonly used one is the radical resection of bladder cancer.[3] However, the radical resection of bladder cancer may be associated with unstable hemodynamics and unbalanced body oxygen supply, which have an influence on the efficiency of radical resection.

Early goal-directed fluid therapy, as a technique used in critical care medicine involving intensive monitoring and aggressive management of perioperative hemodynamics in patients with high-risk of morbidity and mortality, is applied to implement targeted rehydration treatment according to the general condition and volume status of the patients in surgery and can effectively maintain the body's hemodynamic stability and result in good prognosis.[4] In cardiac surgery, goal-directed fluid therapy has proved effective when commenced after surgery, demonstrating a marked decrease in mortality for patients undergoing congenital heart surgery.[5] Furthermore, a reduction in morbidity and mortality has been associated with goal-directed fluid therapy techniques when used in conjunction with an electronic medical record.[6] In addition, early goal-directed therapy is a more specific form of therapy used for the treatment of severe sepsis and septic shock, involving adjustments of cardiac preload, afterload, and contractility to balance oxygen delivery with an increased oxygen demand before surgery.[7] However, the application of goal-directed fluid therapy has not been reported in the radical resection of bladder cancer yet. Therefore, we performed this retrospective study to investigate the clinical effect of the goal-directed fluid therapy in elderly patients with radical resection of bladder cancer, aiming at providing a clinical reference for the radical resection of bladder cancer.


 > Materials and Methods Top


Materials

A total of 137 elderly patients treated with radical resection of bladder cancer were selected in the Affiliated Hospital of North China University of Science and Technology (Tangshan, Hebei, China) from October 2012 to October 2014.

Inclusion criteria

All patients were in line with the clinical diagnostic criteria of bladder cancer following the guidelines of diagnosis and treatment for common cancers in China [8] and were confirmed by clinical manifestations and laboratory and imaging examinations.

Exclusion criteria

Patients with other organic diseases, hematologic diseases, immune diseases, infectious diseases, mental diseases, surgical contraindications, or allergic constitution were excluded from the study.

After screening, 76 patients were finally enrolled in this study. Grouping was performed applying simple random, hidden, and single-blind method. According to random number table, 76 patients were randomly numbered as 01–76; the control group was selected by reading 38 random numbers starting at the second row and the fifth column of the random number table from left to right, with automatic skip for the number >76 or repeated numbers, and the rest patients were grouped as the observation group. Among the control group, there were 28 males and ten females, aging 61–72 (65.2 ± 3.8) years and weighing 42–69 (56.4 ± 5.1) kg. The operative time for the control group was 184–253 (203.6 ± 17.5) min and the anesthesia time was 269–324 (298.7 ± 13.6) min. The primary diseases for the control group included 21 cases of transitional cell carcinoma, eight cases of inverted papilloma, and nine cases of squamous cell carcinoma of the bladder gland. Among observation group, there were 27 males and 11 females, aging 60–73 (65.6 ± 3.7) years and weighing 41–68 (56.3 ± 4.8) kg. The operative time for the observation group was 180–258 (202.9 ± 23.6) min and the anesthesia time was 273–340 (301.5 ± 17.4) min. The primary diseases for the observation group included 20 cases of transitional cell carcinoma, seven cases of inverted papilloma, and 11 cases of squamous cell carcinoma of the bladder gland. The differences of the baseline characteristics for both groups (age, sex, weight, anesthesia time, operation time, blood loss, etc.) were not statistically significant (P > 0.05) but comparable. This research had enabled the approval of the patient's family, and an informed consent had been signed by the patients and passed by the Hospital Ethics Committee.

Methods

The patients in the control group were treated routinely. The radial artery puncture was implemented under local anesthesia, and Doppler ultrasound-guided (Midwest Yuanda Technology Co., Ltd., Beijing, China; SKK24-S6 xk/1) internal jugular vein catheterization was carried out before the induction of anesthesia medication so as to use Philips MP40 multi-function monitor (Shanghai Huaxi Medical Instrument Company Limited, Shanghai, China) and Sonoclot analyzer (Sienco Inc., Morrison, CO, USA) to obtain related data and parameters and in addition FloTrac/Vigileo monitoring system 1.10 (Edwards Lifesciences, Irvine, California, USA) to obtain relevant hemodynamic indexes including stroke volume (SV), SV index (SVI), and SV variation (SVV). All patients in the control group received anesthesia induction with endotracheal intubation through successively slow intravenous injection of propofol (1.5 mg/kg; Beijing Fresenius Kabi Pharmaceutical Co., Ltd., Beijing, China), fentanyl (4 μg/kg; Yichang Humanwell Pharmaceutical Co., Ltd., Hubei, China), and rocuronium (0.6 mg/kg; Beijing Yikangsida Medical Technology Co., Ltd., Beijing, China). After endotracheal intubation, mechanical ventilation was conducted with intraoperative respiratory parameters adjusted according to blood oxygen saturation (98–100%) and partial pressure of carbon dioxide in end-expiratory gas (35–45 mmHg). Anesthesia was maintained by intraoperative target-controlled infusion of propofol and remifentanil (Yichang Humanwell Pharmaceutical Co., Ltd., Hubei, China), and the plasma target concentration of propofol was preliminarily set at 2–4 μg/ml whereas of remifentanil at 2–3 ng/ml. Muscle relaxation was maintained by continuous infusion of 0.5–0.75 mg/kg/h atracurium. Intraoperatively, entropy index was maintained at 40–60; the fluctuation of mean arterial pressure (MAP) and heart rate (HR) was not more than 20% of base value. Patients of the control group were treated with the volume therapy in traditional infusion process. Compound sodium lactate (5–7 ml/kg; Xuzhou No. 5 Pharmaceutical Factory Co., Ltd., Jiangsu, China) was infused before anesthesia for compensatory intravascular volume expansion. Suitable state received any treatments. Compound sodium lactate (500 ml) was infused when MAP was lower than 65 mmHg, and central venous pressure (CVP) was lower than 0.6 mmHg, followed by an infusion of 250 ml hydroxyethyl starch injection (Beijing Fresenius Kabi Pharmaceutical Co., Ltd., Beijing, China) for uncontrolled. Patients received dobutamine treatment (Shanghai No. 1 Biochemical Pharmaceutical Company, Shanghai, China) when CVP was higher than 1.0 mmHg and MAP was lower than 65 mmHg.

Based on the conventional therapy, patients of the observation group were treated with the goal-directed fluid therapy. Compound sodium lactate (5–7 ml/kg) was infused before anesthesia. Patients received any treatment when cardiac output index was higher than 2.5 L.min -1.m 2; MAP was higher than 65 mmHg, and SVI was higher than 35 ml/m 2. An infusion of 250 ml hydroxyethyl starch injection was performed combined with dobutamine treatment for the patients with cardiac output index lower than 2.5 L.min -1.m 2, SVI lower than 35 ml/m 2, and SVV lower than 12%. After the infusion of compound sodium lactate (500 ml), changes in SVV were observed, followed by direct treatment of dobutamine if cardiac output index was lower than 2.5 L.min -1.m 2 and SVI was higher than 35 ml/m 2.

Postoperatively, patients in both groups underwent patient-controlled vein analgesia with the loading dose of fentanyl (0.5 μg/kg/h) at 50 μg and patient-controlled intravenous analgesia locking time of 15 min. Efficiency and complications were observed and recorded every day from patients undergoing operation to discharging from hospital.

Observation targets

There were 5 time-points (T0, T1, T2, T3, and T4) for the observation of the patients: T0 was observed after the establishment of monitoring; T1 was observed after the anesthesia intubation; T2 was observed at the start of the surgery; T3 was observed 1 h after the surgery; T4 was observed at the end of the surgery. All the 5 time-points were observed to monitor the change of the following indexes: (1) hemodynamic indexes (HR, cardiac output, stroke variability, MAP, and CVP); (2) fluid volume changes (bleeding volume, urine volume, colloidal fluid volume, liquid crystal volume, and total input volume); (3) related-metabolism indexes (central venous oxygen saturation, arterial serum lactate, S100-β, oxygen supply index, oxygen consumption index, and oxygen uptake rate); (4) postoperative complications (nausea and vomiting, hypotension, arrhythmia, infection and delirium); (5) therapeutic effects (postoperative flatus time, postoperative food-taking time, length of stay, and expenses) which were followed up from the end of the operation to patients discharging from hospital.

Statistical analysis

The SPSS 21.0 software (SPSS Inc., Chicago, IL, USA) was used for the statistical analysis, and the measurement data were represented as mean ± standard deviation (x̄± s) and verified by Kolmogorov–Smirnov test; the measurement data consistent with normal distribution were detected by group t-test for the comparison of independent sample between two groups. In addition, the comparison of multiple samples was conducted by using analysis of variance. The counting data were represented as rate (%) and detected by Chi-square test. P < 0.05 was considered statistically significant.


 > Results Top


Random grouping

A total of 137 elderly patients with bladder cancer were admitted to the Affiliated Hospital of North China University of Science and Technology; among them, nine patients had venous thrombosis, five had coronary heart disease, three had rheumatoid heart disease, five had gastric ulcer, seven had hepatocirrhosis, two had toxic hepatitis, four had pulmonary tuberculosis, 12 had diabetes, three had rheumatoid arthritis, six had thyroid function hyperthyroidism, and five had sensitive constitution [Figure 1]. Therefore, a sum of 61 patients was excluded and 76 patients were finally included. In addition, the 76 patients were grouped according to random number table into the control group and the observation group, with 38 patients in each group.
Figure 1: Inclusion and grouping for included patients with bladder cancer

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Comparison of the hemodynamics index for both groups at different time points

The HR difference of both groups at different time-points of T0, T1, T2, T3, and T4 was not statistically significant and the differences of cardiac output index, stroke variability, MAP, and CVP at the time-point of T0 were not statistically significant as well (all P > 0.05). The cardiac output index, stroke variability, MAP, and central venous pressure at the time-points of T1, T2, T3, and T4 were all significantly higher in the observed group than those in the control group, and their differences were statistically significant (all P < 0.05) [Table 1].
Table 1: Comparison of the hemodynamics index for both groups at different time points (x̄±s)

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Comparison of the fluid volume change for both groups

The difference of bleeding volume for both groups was not statistically significant (P > 0.05). The urine volume and the colloidal infusion volume were apparently higher in the observation group than those in the control group while the crystalloid infusion volume and the total liquid infusion volume were significantly less in the observation group than those in the control group, of which the differences were statistically significant (all P < 0.05) [Table 2].
Table 2: Comparison of the fluid volume change for both groups (x̄±s, ml)

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Comparison of the related metabolic index for both groups

The differences of the central venous oxygen saturation, arterial serum lactate, S100-β, oxygen supply index, oxygen consumption index, and oxygen uptake rate for both groups at the time-point of T0 were all statistically significant (all P > 0.05). The central venous oxygen saturation, oxygen supply index, oxygen consumption index, and oxygen uptake rate observed at the time-points of T1, T2, T3, and T4 were obviously higher in the observation group than those in the control group while the arterial serum lactate and S100-β were apparently lower in the observation group than those in the control group, of which the differences were statistically significant (all P < 0.05) [Table 3].
Table 3: Comparison of the related metabolic index for both groups (x̄±s)

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Comparison of the postoperative complications for both groups

The differences of complication incidence rate in arrhythmia, infection, and delirium for both groups were not statistically significant (all P > 0.05), and the complication incidence rate of nausea, vomiting, and hypotension were sharply lower in the observation group than those in the control group, of which the differences were statistically significant (all P < 0.05) [Table 4].
Table 4: Comparison of the postoperative complications for both groups (n, %)

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Comparison of the therapeutic effect for both groups

The first passage of postoperative flatus time and postoperative food-taking time were significantly earlier in the observation group than those in the control group while the hospitalization time and expenses were obviously less in the observation group than those the control group, of which the differences were statistically significant (all P < 0.05) [Table 5].
Table 5: Comparison of the therapeutic effect for both groups (x̄±s)

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 > Discussion Top


As the most common malignant tumor of the urinary system, bladder cancer has a higher morbidity, especially among the elder people,[9],[10] and the radical resection of bladder cancer is a common surgical resection with a wider scope of surgery operation.[11] The fluid management during the surgery procedure is particularly important while the conventional fluid management requires an advanced preset of the fluid volume which therefore is unable to meet individual needs and also increases the risk of inadequate tissue perfusion, organ dysfunction, and other adverse events. However, the goal-directed fluid therapy is totally different. Based on the perioperative systemic volume status and detailed hemodynamic parameters, the fluid management of the goal-directed fluid therapy can implement an effective individualized rehydration solution which can maintain a better hemodynamic stability so as to ensure a smooth operation and thereby improve the prognosis of the patients.[12]

The FloTrac/Vigileo system, which is used for monitoring the cardiac output volume detected through the arterial pressure [13] and analyzed the arterial pressure waveform obtained through the arterial artery and femoral artery catheter so as to implement an indirect measurement of the cardiac output volume or other hemodynamic parameters, is simple in operation, less in trauma, and dominant in continuous acquisition of hemodynamic index. The results of this research declared that the cardiac output index, stroke variability, MAP, and CVP observed in each time-point of anesthesia and surgery of the patients were significantly higher in the observation group than those in the control group, and the fluctuation range of related indexes was smaller, indicating that the hemodynamic index of the patients in the observation group was more stable. The central venous oxygen saturation, oxygen supply index, oxygen consumption index, and oxygen uptake rate observed in the time-points of T1, T2, T3, and T4 of the patients were obviously higher in the observation group than those in the control group, declaring that a higher level of oxygen supply was conducted in the observation group and an effective balance of oxygen supply and oxygen consumption was maintained in the body. Although goal-directed fluid therapy has not been reported in the radical resection of bladder cancer, it has been used in some other surgeries and gained similar results; for instance, Scheeren et al. suggested that a goal-directed strategy might decrease postoperative organ dysfunction [14] and Cecconi et al. found that goal-directed fluid therapy is beneficial in all high-risk patients undergoing major surgery in terms of hemodynamics and body oxygen supply and confirmed the mortality benefit of goal-directed fluid therapy.[15]

Lactate dehydrogenase is one of the important enzymes in anaerobic glycolysis and gluconeogenesis, accelerating the oxidation and reduction reaction between pyruvate and L-lactate, as well as α-oxoacid catalyzed by monitoring arterial serum lactate to analyze the anaerobic metabolism status of the patients. As one kind of calcium-binding protein, S100-β protein mainly distributes in astrocytes and Schwann cells which normally can only generate a small amount of S100-β protein that can hardly pass through the blood–brain barrier (BBB), so the S100-β protein content in the blood is extremely low. However, after the brain injury, the astrocytes can release reasonable amount of S100-β protein which can create BBB damage and increase permeability so that the S100-β protein content can be elevated significantly.[16] Therefore, the cerebral oxygen metabolism and the brain damage of the patients can be monitored through the observation of the S100-β volume. The results of this research demonstrated that the arterial serum lactate and S100-β protein were significantly lower in the observation group than those in the control group, which indicating that a good oxygen supply was maintained in the patients of the observation group, and no significant anaerobic metabolism and brain injury were observed.

The stroke variability, which is an important feature of hemodynamic indexes for monitoring the volume status of the patients on mechanical ventilation and forecasting the body's response to the fluid therapy, is dominant in sensitivity, accuracy, and security.[17] Better results were obtained by applying the stroke variability in goal-directed fluid therapy to predict the volume response of the patients on mechanical ventilation. The colloidal and the crystalloid volumes should not be considered to be simply alternative because the crystalloid supply for the volume loss in blood vessels could result in massive remaining of the crystalloid outside the blood vessels, increasing the risk of tissue edema, hypotension, delayed healing, and pneumonia which were not conducive to the recovery of the patients.[18] The colloidal solution was not always rational as well, for the extensive use of which could result in various degrees of renal impairment and affect blood coagulation. Therefore, a good treatment required an appropriate consideration of the indications and contraindications of medicines by applying a rational usage of medicine dosage to ensure a better treatment effect as well as a superior security. The goal-directed fluid therapy proceeded to maintain a normal range of stroke variability, HR, and blood pressure of the patients by monitoring the demand of fluid infusion for the patients and focusing on the usage of colloidal solution which was proved to be effective. The results of this research indicated that the urine and the colloidal volumes of the patients were significantly more in the observation group than those in the control group while the crystalloid and the total fluid input volumes were apparently less in the observation group than those in the control group, which declaring that the observation group not only effectively maintained the body's hemodynamic stability but also ensured good tissue perfusion and reasonable colloid infusion and crystalloid infusion volumes. The differences of complication incidence rate in arrhythmia, infection, and delirium for both groups were not statistically significant. The complication incidence rate of nausea, vomiting, and hypotension was sharply lower in the observation group than those in the control group, which demonstrating that the goal-directed fluid therapy was safe and effective with less complications and superior security. In line with our study, Dalfino et al. demonstrated that the goal-directed fluid therapy designed to optimize oxygen delivery protects surgical patients against postoperative hospital-acquired complications and must be strongly encouraged, particularly in the high-risk surgical population.[19]

In terms of treatment effect, the first passage of postoperative flatus and postoperative food-taking times were significantly earlier in the observation group than those in the control group while the hospitalization time and expenses were obviously less in the observation group than those in the control group, indicating that the goal-directed fluid therapy could in some degrees improve the prognosis of the patients and reduce the therapeutic time and expenses at the greatest extent for the patients to accept easier.


 > Conclusion Top


The goal-directed fluid therapy is worthy of clinical expansion, for it can stabilize hemodynamic status, maintain oxygen balance of supply and demand, guarantee good microcirculation perfusion, reduce therapeutic time and expenses, and decrease complications and superior security. These results provide a clinical reference for the treatment of bladder cancer with radical resection. The inadequacy of small sample size and sources of potential bias, imprecision, and multiplicity in this research requires further expansion of the sample size and further well-designed study of the goal-directed fluid therapy as an optional fluid management program for the elderly patients with bladder cancer.

Acknowledgments

We would like to acknowledge the reviewers for their helpful comments on this study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

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Jacobs BL, Daignault S, Lee CT, Hafez KS, Montgomery JS, Montie JE, et al. Prostate capsule sparing versus nerve sparing radical cystectomy for bladder cancer: Results of a randomized, controlled trial. J Urol 2015;193:64-70.  Back to cited text no. 1
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National Office for Cancer Prevention and Control. Guidelines of Diagnosis and Treatment for Common Cancers in China [M]. Beijing: The Joint Publishing Company of the Beijing Medical University and the Peking Union Medical University; 1990.  Back to cited text no. 8
    
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Gandaglia G, Popa I, Abdollah F, Schiffmann J, Shariat SF, Briganti A, et al. The effect of neoadjuvant chemotherapy on perioperative outcomes in patients who have bladder cancer treated with radical cystectomy: A population-based study. European urology 2014;66:561-8.  Back to cited text no. 9
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