Int J Clin Pharm (2015) 37:379–386 DOI 10.1007/s11096-015-0072-9
RESEARCH ARTICLE
Reduced length of stay in radical cystectomy patients with oral versus parenteral post-operative nutrition protocol Peter Declercq • Gunter De Win • Frank Van der Aa • Beels Elodie • Lorenz Van der Linden • Hendrik Van Poppel • Willems Ludo • Spriet Isabel
Received: 6 June 2014 / Accepted: 27 January 2015 / Published online: 10 February 2015 Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie 2015
Abstract Background In Europe, parenteral nutrition is often used after radical cystectomy to avoid postoperative malnourishment. To the best of our knowledge, however, there is a paucity of data to conclude on the best modality for delivering nutritional support to this patient group. Objective The parenteral nutrition policy was reconsidered and an oral nutrition protocol was implemented by the clinical pharmacist and evaluated in terms of length of stay, number and type of postoperative complications and parenteral nutrition avoided costs. Setting A prospective interventional non-randomized before-after study was conducted. Regular radical cystectomy patients presenting without preoperative contra-indications for enteral nutrition were eligible. Methods Postoperatively, in the control group, the parenteral nutrition policy from the ward was applied. Parenteral nutrition was initiated systematically and continued until the patient was able to tolerate solid food. In the interventional group, an oral nutrition
P. Declercq (&) L. Van der Linden W. Ludo S. Isabel Pharmacy Department, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium e-mail: [email protected] P. Declercq L. Van der Linden W. Ludo S. Isabel Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium G. De Win F. Van der Aa B. Elodie H. Van Poppel Department of Urology, Faculty of Medicine, University Hospitals Leuven, Leuven, Belgium G. De Win F. Van der Aa B. Elodie H. Van Poppel Department Development and Regeneration, KU Leuven, Leuven, Belgium G. De Win Department of Urology, Faculty of Medicine, University Hospital Antwerp, Antwerp, Belgium
protocol was implemented. Parenteral nutrition could be initiated if oral intake remained insufficient after 5 days. Main outcome measure The primary end point was postoperative length of stay. Secondary endpoints included the number of patients in whom the oral nutrition protocol was implemented successfully, as well as the number and type of postoperative complications. Results A total of 94 eligible patients was assigned consecutively to the control (n = 48) and to the interventional group (n = 46). Baseline demographics were comparable. A significant reduction in median length of stay was associated with the oral nutrition protocol [18 days (IQR 15–22) in the control group vs. 14 days (IQR 13–18) in the interventional group (p \ 0.001)]. In 40 out of 46 patients from the interventional group, the oral nutrition protocol was implemented successfully. The number and type of postoperative complications did not differ significantly. Implementing the oral nutrition protocol resulted in a direct parenteral nutrition infusion bag cost saving of approximately €512 and a reduction in hospitalization cost of €2,608 per patient. Conclusion The findings of our study showed that an oral nutrition protocol, when compared to the systematic postoperative use of parenteral nutrition, was associated with a decreased length of stay and costs in a regular radical cystectomy patient population. Keywords nutrition
Belgium Costs Length of stay Oral
Abbreviations CFU Colony forming units CRBSI Catheter related blood stream infection EN Enteral nutrition ONP Oral nutrition protocol POI Postoperative ileus POCs Postoperative complications
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PN RC
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Parenteral nutrition Radical cystectomy
Impact of findings on practice statements •
•
•
•
There is a paucity of data to conclude that systematic parenteral nutrition use is the best modality for delivering nutritional support after regular radical cystectomy. The introduction of an oral nutrition protocol by the clinical pharmacist attached to the urology ward was associated with a decreased length of stay and a substantial decrease in parenteral nutrition associated costs. Our findings showed that an oral nutrition protocol is a valid and safe alternative for systematic use of parenteral nutrition after regular radical cystectomy. These findings are relevant in guiding clinicians when deciding on which type of nutritional support should be pursued after radical cystectomy.
Introduction Currently, bladder cancer and neurogenic bladder problems can be treated by radical cystectomy (RC) and immediate urinary diversion. Postoperative, delayed return of bowel function is relatively common, with rates ranging from 0.8 to 20 % [1–7]. Consequently, delay in oral nutritional intake can be associated with prolonged recovery and hospital stay [1, 4, 5]. In Europe, parenteral nutrition (PN) is often used after RC to prevent patients from becoming malnourished [1]. However, there is a paucity of data to conclude on the best modality for delivering nutritional support to this patient group. In uretero-ileal and ileo-ileal anastomosis, both carried out after RC, enteral nutrition (EN) is not contra-indicated [8]. Moreover, compared to PN, EN is associated with fewer complications and costs [1, 6, 9–11]. Therefore, systematic use of PN after regular RC should be evaluated in terms of safety and costs [1]. Aim of the study The impact of an oral versus parenteral nutrition protocol on postoperative length of stay (LOS), postoperative complications (POCs) and costs was investigated in a regular RC population. Ethical approval The study was approved by the hospital’s ethics committee and registered on clinical trials.Gov No. NCT01777126.
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No informed consent was obtained as the introduction of the ONP was part of continuous improvement of standard of care in our hospital.
Method Design A prospective interventional non-randomized before-after trial was conducted. Patients were consecutively assigned to the control group until the predefined sample size was reached. After enrollment and follow-up of control patients had been finished, all newly admitted eligible patients were consecutively assigned to the interventional group. In addition to the before-after study, a sample of eligible patients was collected from March 2011 to March 2013 (follow-up group) to examine the post-study impact of the ONP. Patients All adult patients admitted to the 48-bed urological ward in the 1,850 bed University Hospitals Leuven and treated with elective regular RC were eligible. Three different diversions are performed: an ileal conduit, an orthothopic neobladder (N-pouch) or a continent cutaneous diversion [12]. The surgical procedure was considered regular if the patient returned after the procedure to the urological ward and was not transferred to the intensive care unit (ICU). None of the patients received (neo) adjuvant chemotherapy. Exclusion criteria were transfer to the ICU and preoperative contra-indications for EN. Contra-indications for EN were intestinal obstruction, malabsorption, multiple high-output fistula or intestinal ischemia [8]. Uretero–ileal or ileo-ileal anastomoses, resulting from RC, were not considered as contra-indications for EN [9, 10]. Protocol Preoperatively, all patients received bowel preparation with a 2 l osmotic laxative (macrogol 3,350 100 g, sodiumsulphate 7.5 g, NaCl 2.69 g, KCl 1.02 g, sodium salt of ascorbic acid 5.9 g and ascorbic acid 4.7 g). Before incision, a loading dose of 0.05 ml/cm epidural analgesics (levobupivacaine 2, 5 mg/ml and sufentanil 1 mcg/ml) was administered. During surgery, a central venous catheter, a nasogastric or percutaneous gastrostomy tube and ureteral stents (US) were inserted. The nasogastric or percutaneous gastrostomy tube was removed on the first or second postoperative day after restoration of transit, i.e. a residual gastric volume \50 ml/24 h. Acetaminophen, non-steroidal anti-inflammatory drugs and patient-controlled
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epidural analgesia (levobupivacaine 2, 5 mg/ml and sufentanil 1 mcg/ml) were available for postoperative acute pain management. Intraoperative antimicrobial prophylaxis consisted of cefazoline and metronidazole. Thromboprophylaxis consisted of enoxaparin. Anti-emetics and other prokinetic drugs were not routinely administered but only prescribed when needed. All treating surgeons were fully trained at the start of the study. After a minimum of 10 days and after restoration of transit, presence of bowel movements and absence of fever (defined as body temperature \38.3 C), US were removed. Prophylactic levofloxacin 500 mg once daily was administered after stent removal. Patients were discharged if the following four criteria were fulfilled: (1) removal of all drains and stents, (2) the absence of fever, (3) the ability to tolerate solid food and (4) the ability of independent mobilization. Care practices (anesthesia modalities, surgical techniques, doses of narcotics, bowel stimulants and anti-nauseants, and mobilization practices) did not alter during the course of the study. In the control group, PN was initiated immediately after surgery and continued until toleration of solid food (i.e. the standard of care PN policy from the ward). PN infusion therapy consisted of a parenteral solution with a total energy of 1,100 kcal/1,000 ml and containing polyaminoacids (43.75 g/1,000 ml), glucose (140 g/1,000 ml), lipids (40 g/1,000 ml) and electrolytes. Multivitamin powder and trace elements for injection were added daily to the PN. The amount of PN administered depended on the nonprotein requirements, calculated by 30 ± 10 % kcal/kg ideal body weight [13]. Extra fluids, up to 2 l/day, were given intravenously, at the discretion of the treating physician. In the interventional group, an oral nutrition protocol (ONP), developed by the clinical pharmacist in collaboration with the urologists and dieticians, was implemented (Table 1). Oral intake was increased progressively with oral fluids and easily digestible food, independent of bowel movements. Extra fluids, up to 2 l/day, were given intravenously at the discretion of the surgeon. Nurses verified daily whether the patient was able to tolerate the ONP. From the sixth day, the patient was allowed to eat at will. Only if oral intake remained insufficient after 5 days, PN could be initiated in this group. Data collection Baseline demographic data were retrieved from medical files: patient characteristics [gender, age, weight, length, BMI, age-adjusted Charlson comorbidity index, oncologic or neurogenic indication and bladder cancer staging (TNM classification)], surgical aspects (type of urinary diversion,
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surgeon, intra-operative blood loss and duration of procedure), postoperative ileus (POI) and day of nasogastric tube (NGT) removal [14, 15]. The age-adjusted Charlson comorbidity index is a method for classifying comorbid conditions. POI was defined as the inability to tolerate solid food, the need to place a nasogastric tube in suction, the need to stop oral intake due to abdominal distention, nausea or emesis. Endpoints The primary endpoint was LOS from surgery to discharge. Secondary endpoints were the number of patients with successful implementation of the ONP, as well as number of administered PN infusion bags per patient, time to resumption of full diet, number of patients with one or more postoperative complications (POC), number of POCs per patient, type and severity grade of POCs according to the Clavien-Dindo classification and the incidence of catheter related bloodstream infections (CRBSIs) [16]. The implementation of the ONP was considered successful if the protocol could be applied and no PN was needed. CRBSI, a common PN-related complication, was defined as bacteremia or fungemia in a patient having an intravascular device and more than one positive blood culture result obtained from a peripheral vein, clinical manifestations of infection (e.g. fever, chills, and/or hypotension) and no apparent other source for blood stream infection [6, 17]. Post-study impact An additional patient cohort was assembled, using the same inclusion and exclusion criteria. The LOS and number of PN infusion bags after surgery were determined and compared to the results obtained from the intervention group. Analysis of savings For this cost saving analysis, we looked into avoided costs for non-administered PN infusion bags and into the avoided costs for the reduction in hospitalization days on the Urology services of the University Hospitals Leuven. The cost savings for non-administered PN infusion bags, was calculated taking into account €60/PN infusion bag. For every group, the total number of PN infusion bags was divided by the number of patients and multiplied by €60. This resulted in a direct and comparable PN infusion bag related cost per patient per group. In Belgium, the daily hospitalization cost for an acute service, such as the Urology ward, in a university hospital is €652/day.
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Table 1 Postoperative oral nutrition protocol (ONP) Post cystectomy
Breakfast
Lunch
Dinner
Day 1
1 bottle of still water
1 cup of lime tea with sugar, honey and lemon (50 kcal)
1 cup of lime tea with sugar, honey and lemon (50 kcal)
OR
OR
1 glass of still water
1 glass of still water
IV FLUID MANAGEMENT Up to two litres, depending on oral fluid intake Day 2
Oral fluids at the discretion of the patient
IV FLUID MANAGEMENT
(same fluids as on Day 1)
Up to two litres, depending on oral fluid intake Day 3
Yoghurt (60 kcal)
Stock broth (20 kcal)
Yoghurt (60 kcal)
IV FLUID MANAGEMENT
?
?
?
Up to two litres, depending on oral fluid intake
Oral energy sips (300 kcal)
Oral energy sips (300 kcal)
Oral energy sips (300 kcal)
Day 4
Toast with jam (105 kcal)
Poached fish ? butter dressing ? mashed potatoes (500 kcal)
Slices of white bread
Chicken ? applesauce ? mashed potatoes ? pudding
Slices of white bread
IV FLUID MANAGEMENT
(150 kcal)
Up to two litres, depending on oral fluid intake Day 5
Slices of white bread
IV FLUID MANAGEMENT
(150 kcal)
(150 kcal)
(550 kcal)
Up to two litres, depending on oral fluid intake Day 6
Regular diet
IV FLUID MANAGEMENT
OR
Up to two litres, depending on oral fluid intake
If the patient cannot meet energy requirements by mouth on the 6th day and has a CI for EN, start PN Energy requirements (kcal/day) = 30 kcal/kg ideal body weight * [14] ± 10 % *
Male BMI \ 30: 50 ? 0,91 9 (length (cm) -152,5)
*
Male BMI C 30: 1,2 9 [50 ? 0,91 9 (length (cm) -152,5)] Female BMI \ 30: 45,5 ? 0,91 9 (length (cm) -152,5)
* *
Female BMI C 30: 1,2 9 [45,5 ? 0,91 9 (length (cm) -152,5)]
Postoperative oral nutrition protocol (ONP) (IV intravenous, CI contra-indication, EN enteral nutrition, PN parenteral nutrition, kcal kilocalories, BMI body mass index)
Statistical analysis Statistical analysis was performed by L-Biostat, Catholic University Leuven, using SPSS Statistics 20.0 for Windows. Chi square and Fisher’s Exact tests were used for categorical data. The unpaired t test or the Wilcoxon rank sum test was used for normal and non-normal distributed continuous variables respectively. Baseline demographic data and outcome measures were considered statistically significant if p-values were \0.05. The Bonferroni correction was used to account for multiple comparisons (six secondary outcome measures). Therefore, secondary outcome parameters were considered statistically significant if p-values were \0.008. To asses factors influencing LOS, general linear model statistics—univariate analysis followed by ANOVA—were carried out. Preliminary data from our institution showed that all RC patients received PN directly after surgery and were discharged
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after a mean of 19.3 ± 5.6 days. We expected to reduce our LOS with 3 days from 19 to 16 days by implementing the ONP. Assuming that variances for both groups are comparable, 88 (2 9 44) patients were needed, giving at least 80 % power (a = 0.05, one-tailed) to reject the null hypothesis defined as no difference in postoperative LOS between both groups.
Results During the 2 year study period (01/02/2009–10/03/2011), 104 patients, all admitted to the urology ward, underwent RC. Ten patients were excluded: 7 patients needed a postoperative ICU transfer and 3 patients had preoperative contra-indications for EN. From 01/02/2009 to 25/02/2010, 48 patients were consecutively included in the control group. Between 15/03/2010 and 10/02/2011, 46 patients were consecutively included in the interventional group.
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After completion of the original study, 114 patients were included in the follow-up group (11/03/2011–10/03/2013). Baseline demographics Baseline demographics, surgical aspects, POI and NGT removal day were comparable for both groups (Table 2). POI occurred in 9/48 patients in the control group and in 13/46 patients in the interventional group (p = 0.334; Table 2). The attending surgeons differed between the two groups (p = 0.04; Table 2). Endpoints A significant reduction in the median postoperative LOS from 18 days (IQR: 15–22 days) in the control group to 14 days (IQR: 13–18 days) in the interventional group (p \ 0.001) was observed (Table 3). In 40 out of 46 (87 %) patients from the interventional group, the ONP was implemented successfully. In seven out of those 40 patients, symptoms of POI resolved before the fourth day and therefore full diet could be resumed on the fourth day. Due to prolonged POI leading to insufficient oral caloric intake on the sixth postoperative day, the remaining 6 patients of the 46 patients received PN starting postoperatively on day six. Every patient in the control group received PN with a total of 435 PN infusion bags (median of eight [6, 10] PN infusion bags) versus 6/46 patients in the interventional group with a total of 24 PN infusion bags [median of 0 (0; 0) PN infusion bags] (p \ 0.001). The median time to resumption of full diet was significantly shorter in the interventional group versus the control group [4 [3, 5] days vs. 8 [6, 10] days, respectively (p \ 0.001)] (Table 3). Between both groups, there was no difference in the number of patients with POCs (p = 0.487) and the median amount of POCs per patient (p = 0.302) (Table 3). The type and the severity grade of POCs did not differ significantly (p = 0.049 and p = 0.698; Table 3) and there was no need for surgical re-intervention in any of the patients. Four patients in the control group versus none in the interventional group developed clinical manifestations of CRBSI (p = 0.117). The two statistically significantly different parameters, i.e. the involved surgeon and the allocation to the ONP protocol, were retained for the general linear model with LOS as dependent variable. This analysis showed a significant difference in LOS in the intervention versus control group (p \ 0.001), which remained significant after correcting for the operating surgeon. Post-study impact After study completion, 114 patients were admitted for regular RC. The median postoperative LOS was 15 days
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(13–20 days) and PN was administered in 13 patients with a total of 91 PN infusion bags. Both outcomes did not differ with those from the interventional group (p = 0.169 and p = 0.760). Analysis of PN costs In the control group a total of 435 PN bags were administered in 48 patients. Hence, the cost per patient was 435x €60/bag divided by 48 patients = €544/patient. In the interventional group a total of 24 parenteral nutrition infusion bags was administered in 46 patients. Conversely, the cost per patient was 24 9 €60 divided by 46 patients = €31/patient. The netto PN cost saving per patient for the hospital budget is thus €544 – €31 = €512. By reducing the median LOS with 4 days, the cost savings were 4 9 €652/day = €2,608/patient. Hence based on avoided costs, the implementation of the oral nutrition protocol was associated with a cost saving of €512 ? €2,608 = €3,120/patient.
Discussion In many centers in Europe, especially in those with governmental reimbursement for PN, PN is standard of care after RC. Our study shows that implementation of the ONP is associated with a decreased postoperative LOS as compared to systematic postoperative PN therapy. Implementation of an ONP is also associated with a reduction in administered PN infusion bags, a faster resumption of oral diet, but no difference in POCs. Furthermore, cost savings after initiating the ONP were €3,120/patient. Our data concerning LOS corroborate data from literature. On the one hand, the median baseline LOS of 18 days (IQR 15–22 days), which is the LOS in our PN group, is in line with previously reported LOS in RC patients: i.e. 21–23 days, all expressed as mean LOS [18–20]. On the other hand, in our study population, implementation of the ONP was associated with a reduction in LOS to a median of 14 [13, 18] days, as was also reported by research groups investigating enhanced recovery pathways in RC patients [5–7]. However, it is important to mention that historically LOS in Europe has always been longer than in North America. In North America, the standard use of ONP, early recovery pathways and streamlining recovery by limiting the use of parenteral medications and NGT have significantly shortened LOS. Therefore, effects on LOS may not be generalizable to North American practice. Despite POI being rather prevalent in this population, the interventional group resumed full diet significantly faster [1–7, 21]. This is explained by early initiation of the ONP and the associated stimulation of early resumption of
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Table 2 Baseline demographics
Control group (n = 48)
Interventional group (n = 46)
Males
31 (65 %)
34 (74 %)
Females
17 (35 %)
12 (26 %)
p-value
Gender
Age (y)b
66.0 (55–75)
65.5 (57–72.5)
NS (p = 0.856)
Weight (kg)a
73.7 ± 13.9
75.4 ± 14.2
NS (p = 0.563)
Length (cm)a
169.7 ± 8.2
170.8 ± 8.0
NS (p = 0.513)
BMI (kg/m2)a
25.5 ± 4.0
25.8 ± 4.3
NS (p = 0.765)
Age-adjusted Charlson comorbidity indexb
4 (3–5)
5 (3–6)
NS (p = 0.661)
Neurogenic
9 (19 %)
6 (13 %)
Oncologic
39 (81 %)
40 (87 %)
Indication for surgery
NS (p = 0.576)
Bladder cancer staging (TNM classification) Non oncologic
7 (15 %)
NS (p = 0.328) 5 (11 %)
T1N0M0
3 (6 %)
2 (4 %)
T1N ? M0
2 (4 %)
1 (2 %)
T2-3N0M0
20 (42 %)
15 (33 %)
T2-3N ? M0
8 (17 %)
10 (22 %)
T4N0M0
5 (10 %)
2 (4 %)
T4N ? M0
0 (0 %)
2 (4 %)
TisN0M0
3 (6 %)
9 (20 %)
Type of urinary diversion
NS (p = 0.359)
Ileal conduit Orthothopic neobladder
40 (83 %) 6 (13 %)
39 (85 %) 7 (15 %)
Continent cutaneous diversion
2 (4 %)
0 (0 %)
1
5 (10 %)
0 (0 %)
2
19 (40 %)
14 (30 %)
3
5 (10 %)
3 (7 %)
4
19 (40 %)
29 (63 %)
Intra-operative blood loss (ml)b
1,000 (500–1,475)
1,000 (600–1,650)
Duration of procedure (min)b
210 (180–240)
187.5 (180–240)
\0.05 (p = 0.04)
Surgeon
Baseline demographics. (NS not significant, BMI body mass index, POI postoperative ileus, NGT nasogastric tube, IQR interquartile range) a
mean
b
median
Patients with POI 39 (81 %)
33 (72 %)
Yes
9 (19 %)
13 (28 %)
2.0 (1–4.8)
2.0 (1–3)
NGT removal dayb
NS (p = 0.493) NS (p = 0.427) NS (p = 0.334)
No
full diet in the interventional group. This was confirmed by the general linear model. Improvement of nutritional care should belong to the clinical pharmacist’s portfolio as it pertains to the betterment of the individual patient’s care. As surgery is foremost uncomplicated in the majority of cases in regular RC, PN should not remain the standard of care in those patients. Switching PN to oral nutrition might enhance recovery, avoid CRBSI and PN related infections and increase
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NS (p = 0.376)
NS (p = 0.932)
comfort e.g. in terms of mobility for the patient. In our opinion, a thorough systematic evaluation instead of blind introduction of such an ONP, e.g. by initiating the protocol in two phases like we did in a before-after design, was important, as this enables to assess potential differences in complications, LOS and cost. Nevertheless, our study was subjected to potential limitations. First, the major drawback of the design of our study, i.e. a before-after study, is that it does not allow
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Table 3 Primary and secondary outcome measures
Control group (n = 48)
Interventional group (n = 46)
p-value
18 (15–22)
14 (13–18)
p \ 0.001
Primary outcome Time from surgery to dischargea (d) Secondary outcomes PN infusion bags per patient
8 (6–10)
0 (0–0)
p \ 0.001
Time to resumption of full dieta (d)
8 (6–9)
4 (3–5)
p \ 0.001
11 (23 %)
14 (30 %)
37 (77 %)
32 (70 %)
1 (1–2)
1 (0–2)
NS (p = 0.302)
4
0
NS (p = 0.117)
Control group (n = 70)
Interventional group (n = 53)
p-value
21 (30 %)
13 (25 %)
Fistula or leak
1 (1 %)
2 (4 %)
Bleeding or hematoma
5 (7 %)
2 (4 %)
13 (19 %) 13 (19 %)
16 (30 %) 4 (8 %)
Patients with POC
NS (p = 0.487)
No Yes Rate of POCs per patient
a
Patients with CRBSI POCs Type of POC Infection
Primary and secondary outcome measures. In the ‘‘POCs’’, patients with multiple complications are counted more than once. (d day, IQR interquartile range, PN parenteral nutrition, POC postoperative complications, NS not significant, CRBSI catheter related blood stream infection) a
median
Gastro-intestinal Cardiopulmonary
NS (p = 0.049)
Neurologic
0 (0 %)
5 (10 %)
Pain
2 (3 %)
0 (0 %)
Other
15 (22 %)
11 (21 %)
Severity grade of POC
NS (p = 0.698)
Grade I
15 (21 %)
16 (30 %)
Grade II
35 (50 %)
23 (44 %)
Grade III-a
16 (23 %)
12 (23 %)
Grade III-b
4 (6 %)
2 (4 %)
complete comparison for non-observed time-dependent differences between both groups. However, no change was found in type of surgery and care practices (anesthesia modalities, surgical techniques, doses of narcotics, bowel stimulants, anti-emetics and mobilization practices). Furthermore, standard of care is provided as electronic treatment schemes in our hospital, which did not change over time during our study period. In addition, evaluating the impact of the introduction of an ONP in a prospective randomized controlled manner (PRCT) is not easy to carry out. The study was conducted on two urological wards (56 beds in total), led by a team of four urologists, not assigned to a specific ward. Hence, if we would have pursued the PRCT design, results would have been biased due to knowledge on the ONP protocol by the urologists, caring for both the intervention and control patients. Moreover, the results from our post-study follow up analysis were in line with the intervention group and confirmed the associated impact on PN and LOS. Second, differences in preoperative nutrition status might have influenced outcomes. Unfortunately, no routine preoperative nutrition
status screening is performed on the urological wards. Poor preoperative nutrition status has been recognized as a major determinant for developing postoperative complications such as infections and prolonged hospital stay [6, 9, 10, 22]. However, while certainly not conclusive, we retrospectively assessed patient’s BMI values as surrogate marker for nutrition status. Four patients had a BMI \ 18.5, 2 in the control (BMI 17.51 and 17.76) and two in the intervention group (BMI 18.37 and 18.42), respectively. Based on these data we assume that the groups did not differ in terms of number of malnourished patients and that the majority was actually not malnourished at all, which is certainly an extra argument pro implementing an ONP. Third, nutritional outcomes such as daily caloric intake and biochemical markers of nutrition (serum prealbumin, albumin and total protein levels) might have added extra information. Post hoc, we were not able to assess these factors as such. However, as was shown in our follow-up group, the effect on number of infused PN infusion bags and LOS was sustained regardless of nutritional outcomes of the patients. Last, by excluding patients
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with irregular RC or with contra-indications for EN, we cannot extrapolate our results to all RC patients. On the contrary, patients with an irregular cystectomy course would have been transferred to an ICU and subjected to an alternative nutrition protocol. Furthermore, the ONP implies that the oral route is accessible immediately postsurgery, which is intrinsically not achievable in patients with preoperative contra-indications for EN. In summary, we believe that the clinically relevant results of our study are confirming that oral or enteral nutrition should be standard of care in RC patients without contra-indications. Based on our study, the ONP has become now our standard nutrition management after regular RC.
Conclusions Our study showed that an ONP, when compared to the systematic postoperative use of PN, was associated with a decreased LOS and cost in a regular RC patient population. Funding
None.
Conflicts of interest
The authors declare no conflicts of interest.
References 1. Barrass BJ, Thurairaja R, Collins JW, Gillatt D, Persad RA. Optimal nutrition should improve the outcome and costs of radical cystectomy. Urol Int. 2006;77(2):139–42. 2. Hautmann RE, de Petriconi RC, Volkmer BG. 25 years of experience with 1,000 neobladders: long-term complications. J Urol. 2011;185(6):2207–12. 3. Svatek RS, Fisher MB, Williams MB, Matin SF, Kamat AM, Grossman HB, et al. Age and body mass index are independent risk factors for the development of postoperative paralytic ileus after radical cystectomy. Urology. 2010;76(6):1419–24. 4. Adamakis I, Tyritzis SI, Koutalellis G, Tokas T, Stravodimos KG, Mitropoulos D, et al. Early removal of nasogastric tube is beneficial for patients undergoing radical cystectomy with urinary diversion. Int Braz J Urol. 2011;37(1):42–8. 5. Maffezzini M, Campodonico F, Canepa G, Gerbi G, Parodi D. Current perioperative management of radical cystectomy with intestinal urinary reconstruction for muscle-invasive bladder cancer and reduction of the incidence of postoperative ileus. Surg Oncol. 2008;17(1):41–8. 6. Roth B, Birkhauser FD, Zehnder P, Thalmann GN, Huwyler M, Burkhard FC, et al. Parenteral nutrition does not improve postoperative recovery from radical cystectomy: results of a prospective randomised trial. Eur Urol. 2013;63(3):475–82.
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7. Maffezzini M, Gerbi G, Campodonico F, Parodi D. Multimodal perioperative plan for radical cystectomy and intestinal urinary diversion. I. Effect on recovery of intestinal function and occurrence of complications. Urology. 2007;69(6):1107–11. 8. Braga M, Ljungqvist O, Soeters P, Fearon K, Weimann A, Bozzetti F. ESPEN guidelines on parenteral nutrition: surgery. Clin Nutr. 2009;28(4):378–86. 9. Mazaki T, Ebisawa K. Enteral versus parenteral nutrition after gastrointestinal surgery: a systematic review and meta-analysis of randomized controlled trials in the English literature. J Gastrointest Surg. 2008;12(4):739–55. 10. Shrikhande SV, Shetty GS, Singh K, Ingle S. Is early feeding after major gastrointestinal surgery a fashion or an advance? Evidence-based review of literature. J Cancer Res Ther. 2009;5(4):232–9 11. Pruthi RS, Chun J, Richman M. Reducing time to oral diet and hospital discharge in patients undergoing radical cystectomy using a perioperative care plan. Urology. 2003;62(4):661–5. 12. Joniau S, Benijts J, Van Kampen M, De Waele M, Ooms J, Van Cleynenbreugel B, et al. Clinical experience with the N-shaped ileal neobladder: assessment of complications, voiding patterns, and quality of life in our series of 58 patients. Eur Urol. 2005;47(5):666–72 discussion 72-3. 13. Laffey JG, Kavanagh BP. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury. N Engl J Med. 2000;343(11):812. 14. Hall WH, Ramachandran R, Narayan S, Jani AB, Vijayakumar S. An electronic application for rapidly calculating Charlson comorbidity score. BMC Cancer. 2004;4:94 15. Babjuk M, Oosterlinck W, Sylvester R, Kaasinen E, Bohle A, Palou-Redorta J, et al. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder, the 2011 update. Actas Urol Esp. 2012;36(7):389–402. 16. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205–13. 17. Mermel LA, Allon M, Bouza E, Craven DE, Flynn P, O’Grady NP, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2009;49(1):1–45. 18. Louie-Johnsun MW, Braslis KG, Murphy DL, Neerhut GJ, Grills RJ. Radical cystectomy for primary bladder malignancy: a 10 year review. ANZ J Surg. 2007;77(4):265–9. 19. McCabe JE, Jibawi A, Javle P. Defining the minimum hospital case-load to achieve optimum outcomes in radical cystectomy. BJU Int. 2005;96(6):806–10. 20. Malavaud B, Vaessen C, Mouzin M, Rischmann P, Sarramon J, Schulman C. Complications for radical cystectomy. Impact of the American Society of Anesthesiologists score. Eur Urol. 2001;39(1):79–84. 21. Shabsigh A, Korets R, Vora KC, Brooks CM, Cronin AM, Savage C, et al. Defining early morbidity of radical cystectomy for patients with bladder cancer using a standardized reporting methodology. Eur Urol. 2009;55(1):164–74. 22. Gregg JR, Cookson MS, Phillips S, Salem S, Chang SS, Clark PE, et al. Effect of preoperative nutritional deficiency on mortality after radical cystectomy for bladder cancer. J Urol. 2011;185(1):90–6.
RESEARCH ARTICLE
Reduced length of stay in radical cystectomy patients with oral versus parenteral post-operative nutrition protocol Peter Declercq • Gunter De Win • Frank Van der Aa • Beels Elodie • Lorenz Van der Linden • Hendrik Van Poppel • Willems Ludo • Spriet Isabel
Received: 6 June 2014 / Accepted: 27 January 2015 / Published online: 10 February 2015 Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie 2015
Abstract Background In Europe, parenteral nutrition is often used after radical cystectomy to avoid postoperative malnourishment. To the best of our knowledge, however, there is a paucity of data to conclude on the best modality for delivering nutritional support to this patient group. Objective The parenteral nutrition policy was reconsidered and an oral nutrition protocol was implemented by the clinical pharmacist and evaluated in terms of length of stay, number and type of postoperative complications and parenteral nutrition avoided costs. Setting A prospective interventional non-randomized before-after study was conducted. Regular radical cystectomy patients presenting without preoperative contra-indications for enteral nutrition were eligible. Methods Postoperatively, in the control group, the parenteral nutrition policy from the ward was applied. Parenteral nutrition was initiated systematically and continued until the patient was able to tolerate solid food. In the interventional group, an oral nutrition
P. Declercq (&) L. Van der Linden W. Ludo S. Isabel Pharmacy Department, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium e-mail: [email protected] P. Declercq L. Van der Linden W. Ludo S. Isabel Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium G. De Win F. Van der Aa B. Elodie H. Van Poppel Department of Urology, Faculty of Medicine, University Hospitals Leuven, Leuven, Belgium G. De Win F. Van der Aa B. Elodie H. Van Poppel Department Development and Regeneration, KU Leuven, Leuven, Belgium G. De Win Department of Urology, Faculty of Medicine, University Hospital Antwerp, Antwerp, Belgium
protocol was implemented. Parenteral nutrition could be initiated if oral intake remained insufficient after 5 days. Main outcome measure The primary end point was postoperative length of stay. Secondary endpoints included the number of patients in whom the oral nutrition protocol was implemented successfully, as well as the number and type of postoperative complications. Results A total of 94 eligible patients was assigned consecutively to the control (n = 48) and to the interventional group (n = 46). Baseline demographics were comparable. A significant reduction in median length of stay was associated with the oral nutrition protocol [18 days (IQR 15–22) in the control group vs. 14 days (IQR 13–18) in the interventional group (p \ 0.001)]. In 40 out of 46 patients from the interventional group, the oral nutrition protocol was implemented successfully. The number and type of postoperative complications did not differ significantly. Implementing the oral nutrition protocol resulted in a direct parenteral nutrition infusion bag cost saving of approximately €512 and a reduction in hospitalization cost of €2,608 per patient. Conclusion The findings of our study showed that an oral nutrition protocol, when compared to the systematic postoperative use of parenteral nutrition, was associated with a decreased length of stay and costs in a regular radical cystectomy patient population. Keywords nutrition
Belgium Costs Length of stay Oral
Abbreviations CFU Colony forming units CRBSI Catheter related blood stream infection EN Enteral nutrition ONP Oral nutrition protocol POI Postoperative ileus POCs Postoperative complications
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PN RC
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Parenteral nutrition Radical cystectomy
Impact of findings on practice statements •
•
•
•
There is a paucity of data to conclude that systematic parenteral nutrition use is the best modality for delivering nutritional support after regular radical cystectomy. The introduction of an oral nutrition protocol by the clinical pharmacist attached to the urology ward was associated with a decreased length of stay and a substantial decrease in parenteral nutrition associated costs. Our findings showed that an oral nutrition protocol is a valid and safe alternative for systematic use of parenteral nutrition after regular radical cystectomy. These findings are relevant in guiding clinicians when deciding on which type of nutritional support should be pursued after radical cystectomy.
Introduction Currently, bladder cancer and neurogenic bladder problems can be treated by radical cystectomy (RC) and immediate urinary diversion. Postoperative, delayed return of bowel function is relatively common, with rates ranging from 0.8 to 20 % [1–7]. Consequently, delay in oral nutritional intake can be associated with prolonged recovery and hospital stay [1, 4, 5]. In Europe, parenteral nutrition (PN) is often used after RC to prevent patients from becoming malnourished [1]. However, there is a paucity of data to conclude on the best modality for delivering nutritional support to this patient group. In uretero-ileal and ileo-ileal anastomosis, both carried out after RC, enteral nutrition (EN) is not contra-indicated [8]. Moreover, compared to PN, EN is associated with fewer complications and costs [1, 6, 9–11]. Therefore, systematic use of PN after regular RC should be evaluated in terms of safety and costs [1]. Aim of the study The impact of an oral versus parenteral nutrition protocol on postoperative length of stay (LOS), postoperative complications (POCs) and costs was investigated in a regular RC population. Ethical approval The study was approved by the hospital’s ethics committee and registered on clinical trials.Gov No. NCT01777126.
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No informed consent was obtained as the introduction of the ONP was part of continuous improvement of standard of care in our hospital.
Method Design A prospective interventional non-randomized before-after trial was conducted. Patients were consecutively assigned to the control group until the predefined sample size was reached. After enrollment and follow-up of control patients had been finished, all newly admitted eligible patients were consecutively assigned to the interventional group. In addition to the before-after study, a sample of eligible patients was collected from March 2011 to March 2013 (follow-up group) to examine the post-study impact of the ONP. Patients All adult patients admitted to the 48-bed urological ward in the 1,850 bed University Hospitals Leuven and treated with elective regular RC were eligible. Three different diversions are performed: an ileal conduit, an orthothopic neobladder (N-pouch) or a continent cutaneous diversion [12]. The surgical procedure was considered regular if the patient returned after the procedure to the urological ward and was not transferred to the intensive care unit (ICU). None of the patients received (neo) adjuvant chemotherapy. Exclusion criteria were transfer to the ICU and preoperative contra-indications for EN. Contra-indications for EN were intestinal obstruction, malabsorption, multiple high-output fistula or intestinal ischemia [8]. Uretero–ileal or ileo-ileal anastomoses, resulting from RC, were not considered as contra-indications for EN [9, 10]. Protocol Preoperatively, all patients received bowel preparation with a 2 l osmotic laxative (macrogol 3,350 100 g, sodiumsulphate 7.5 g, NaCl 2.69 g, KCl 1.02 g, sodium salt of ascorbic acid 5.9 g and ascorbic acid 4.7 g). Before incision, a loading dose of 0.05 ml/cm epidural analgesics (levobupivacaine 2, 5 mg/ml and sufentanil 1 mcg/ml) was administered. During surgery, a central venous catheter, a nasogastric or percutaneous gastrostomy tube and ureteral stents (US) were inserted. The nasogastric or percutaneous gastrostomy tube was removed on the first or second postoperative day after restoration of transit, i.e. a residual gastric volume \50 ml/24 h. Acetaminophen, non-steroidal anti-inflammatory drugs and patient-controlled
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epidural analgesia (levobupivacaine 2, 5 mg/ml and sufentanil 1 mcg/ml) were available for postoperative acute pain management. Intraoperative antimicrobial prophylaxis consisted of cefazoline and metronidazole. Thromboprophylaxis consisted of enoxaparin. Anti-emetics and other prokinetic drugs were not routinely administered but only prescribed when needed. All treating surgeons were fully trained at the start of the study. After a minimum of 10 days and after restoration of transit, presence of bowel movements and absence of fever (defined as body temperature \38.3 C), US were removed. Prophylactic levofloxacin 500 mg once daily was administered after stent removal. Patients were discharged if the following four criteria were fulfilled: (1) removal of all drains and stents, (2) the absence of fever, (3) the ability to tolerate solid food and (4) the ability of independent mobilization. Care practices (anesthesia modalities, surgical techniques, doses of narcotics, bowel stimulants and anti-nauseants, and mobilization practices) did not alter during the course of the study. In the control group, PN was initiated immediately after surgery and continued until toleration of solid food (i.e. the standard of care PN policy from the ward). PN infusion therapy consisted of a parenteral solution with a total energy of 1,100 kcal/1,000 ml and containing polyaminoacids (43.75 g/1,000 ml), glucose (140 g/1,000 ml), lipids (40 g/1,000 ml) and electrolytes. Multivitamin powder and trace elements for injection were added daily to the PN. The amount of PN administered depended on the nonprotein requirements, calculated by 30 ± 10 % kcal/kg ideal body weight [13]. Extra fluids, up to 2 l/day, were given intravenously, at the discretion of the treating physician. In the interventional group, an oral nutrition protocol (ONP), developed by the clinical pharmacist in collaboration with the urologists and dieticians, was implemented (Table 1). Oral intake was increased progressively with oral fluids and easily digestible food, independent of bowel movements. Extra fluids, up to 2 l/day, were given intravenously at the discretion of the surgeon. Nurses verified daily whether the patient was able to tolerate the ONP. From the sixth day, the patient was allowed to eat at will. Only if oral intake remained insufficient after 5 days, PN could be initiated in this group. Data collection Baseline demographic data were retrieved from medical files: patient characteristics [gender, age, weight, length, BMI, age-adjusted Charlson comorbidity index, oncologic or neurogenic indication and bladder cancer staging (TNM classification)], surgical aspects (type of urinary diversion,
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surgeon, intra-operative blood loss and duration of procedure), postoperative ileus (POI) and day of nasogastric tube (NGT) removal [14, 15]. The age-adjusted Charlson comorbidity index is a method for classifying comorbid conditions. POI was defined as the inability to tolerate solid food, the need to place a nasogastric tube in suction, the need to stop oral intake due to abdominal distention, nausea or emesis. Endpoints The primary endpoint was LOS from surgery to discharge. Secondary endpoints were the number of patients with successful implementation of the ONP, as well as number of administered PN infusion bags per patient, time to resumption of full diet, number of patients with one or more postoperative complications (POC), number of POCs per patient, type and severity grade of POCs according to the Clavien-Dindo classification and the incidence of catheter related bloodstream infections (CRBSIs) [16]. The implementation of the ONP was considered successful if the protocol could be applied and no PN was needed. CRBSI, a common PN-related complication, was defined as bacteremia or fungemia in a patient having an intravascular device and more than one positive blood culture result obtained from a peripheral vein, clinical manifestations of infection (e.g. fever, chills, and/or hypotension) and no apparent other source for blood stream infection [6, 17]. Post-study impact An additional patient cohort was assembled, using the same inclusion and exclusion criteria. The LOS and number of PN infusion bags after surgery were determined and compared to the results obtained from the intervention group. Analysis of savings For this cost saving analysis, we looked into avoided costs for non-administered PN infusion bags and into the avoided costs for the reduction in hospitalization days on the Urology services of the University Hospitals Leuven. The cost savings for non-administered PN infusion bags, was calculated taking into account €60/PN infusion bag. For every group, the total number of PN infusion bags was divided by the number of patients and multiplied by €60. This resulted in a direct and comparable PN infusion bag related cost per patient per group. In Belgium, the daily hospitalization cost for an acute service, such as the Urology ward, in a university hospital is €652/day.
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Table 1 Postoperative oral nutrition protocol (ONP) Post cystectomy
Breakfast
Lunch
Dinner
Day 1
1 bottle of still water
1 cup of lime tea with sugar, honey and lemon (50 kcal)
1 cup of lime tea with sugar, honey and lemon (50 kcal)
OR
OR
1 glass of still water
1 glass of still water
IV FLUID MANAGEMENT Up to two litres, depending on oral fluid intake Day 2
Oral fluids at the discretion of the patient
IV FLUID MANAGEMENT
(same fluids as on Day 1)
Up to two litres, depending on oral fluid intake Day 3
Yoghurt (60 kcal)
Stock broth (20 kcal)
Yoghurt (60 kcal)
IV FLUID MANAGEMENT
?
?
?
Up to two litres, depending on oral fluid intake
Oral energy sips (300 kcal)
Oral energy sips (300 kcal)
Oral energy sips (300 kcal)
Day 4
Toast with jam (105 kcal)
Poached fish ? butter dressing ? mashed potatoes (500 kcal)
Slices of white bread
Chicken ? applesauce ? mashed potatoes ? pudding
Slices of white bread
IV FLUID MANAGEMENT
(150 kcal)
Up to two litres, depending on oral fluid intake Day 5
Slices of white bread
IV FLUID MANAGEMENT
(150 kcal)
(150 kcal)
(550 kcal)
Up to two litres, depending on oral fluid intake Day 6
Regular diet
IV FLUID MANAGEMENT
OR
Up to two litres, depending on oral fluid intake
If the patient cannot meet energy requirements by mouth on the 6th day and has a CI for EN, start PN Energy requirements (kcal/day) = 30 kcal/kg ideal body weight * [14] ± 10 % *
Male BMI \ 30: 50 ? 0,91 9 (length (cm) -152,5)
*
Male BMI C 30: 1,2 9 [50 ? 0,91 9 (length (cm) -152,5)] Female BMI \ 30: 45,5 ? 0,91 9 (length (cm) -152,5)
* *
Female BMI C 30: 1,2 9 [45,5 ? 0,91 9 (length (cm) -152,5)]
Postoperative oral nutrition protocol (ONP) (IV intravenous, CI contra-indication, EN enteral nutrition, PN parenteral nutrition, kcal kilocalories, BMI body mass index)
Statistical analysis Statistical analysis was performed by L-Biostat, Catholic University Leuven, using SPSS Statistics 20.0 for Windows. Chi square and Fisher’s Exact tests were used for categorical data. The unpaired t test or the Wilcoxon rank sum test was used for normal and non-normal distributed continuous variables respectively. Baseline demographic data and outcome measures were considered statistically significant if p-values were \0.05. The Bonferroni correction was used to account for multiple comparisons (six secondary outcome measures). Therefore, secondary outcome parameters were considered statistically significant if p-values were \0.008. To asses factors influencing LOS, general linear model statistics—univariate analysis followed by ANOVA—were carried out. Preliminary data from our institution showed that all RC patients received PN directly after surgery and were discharged
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after a mean of 19.3 ± 5.6 days. We expected to reduce our LOS with 3 days from 19 to 16 days by implementing the ONP. Assuming that variances for both groups are comparable, 88 (2 9 44) patients were needed, giving at least 80 % power (a = 0.05, one-tailed) to reject the null hypothesis defined as no difference in postoperative LOS between both groups.
Results During the 2 year study period (01/02/2009–10/03/2011), 104 patients, all admitted to the urology ward, underwent RC. Ten patients were excluded: 7 patients needed a postoperative ICU transfer and 3 patients had preoperative contra-indications for EN. From 01/02/2009 to 25/02/2010, 48 patients were consecutively included in the control group. Between 15/03/2010 and 10/02/2011, 46 patients were consecutively included in the interventional group.
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After completion of the original study, 114 patients were included in the follow-up group (11/03/2011–10/03/2013). Baseline demographics Baseline demographics, surgical aspects, POI and NGT removal day were comparable for both groups (Table 2). POI occurred in 9/48 patients in the control group and in 13/46 patients in the interventional group (p = 0.334; Table 2). The attending surgeons differed between the two groups (p = 0.04; Table 2). Endpoints A significant reduction in the median postoperative LOS from 18 days (IQR: 15–22 days) in the control group to 14 days (IQR: 13–18 days) in the interventional group (p \ 0.001) was observed (Table 3). In 40 out of 46 (87 %) patients from the interventional group, the ONP was implemented successfully. In seven out of those 40 patients, symptoms of POI resolved before the fourth day and therefore full diet could be resumed on the fourth day. Due to prolonged POI leading to insufficient oral caloric intake on the sixth postoperative day, the remaining 6 patients of the 46 patients received PN starting postoperatively on day six. Every patient in the control group received PN with a total of 435 PN infusion bags (median of eight [6, 10] PN infusion bags) versus 6/46 patients in the interventional group with a total of 24 PN infusion bags [median of 0 (0; 0) PN infusion bags] (p \ 0.001). The median time to resumption of full diet was significantly shorter in the interventional group versus the control group [4 [3, 5] days vs. 8 [6, 10] days, respectively (p \ 0.001)] (Table 3). Between both groups, there was no difference in the number of patients with POCs (p = 0.487) and the median amount of POCs per patient (p = 0.302) (Table 3). The type and the severity grade of POCs did not differ significantly (p = 0.049 and p = 0.698; Table 3) and there was no need for surgical re-intervention in any of the patients. Four patients in the control group versus none in the interventional group developed clinical manifestations of CRBSI (p = 0.117). The two statistically significantly different parameters, i.e. the involved surgeon and the allocation to the ONP protocol, were retained for the general linear model with LOS as dependent variable. This analysis showed a significant difference in LOS in the intervention versus control group (p \ 0.001), which remained significant after correcting for the operating surgeon. Post-study impact After study completion, 114 patients were admitted for regular RC. The median postoperative LOS was 15 days
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(13–20 days) and PN was administered in 13 patients with a total of 91 PN infusion bags. Both outcomes did not differ with those from the interventional group (p = 0.169 and p = 0.760). Analysis of PN costs In the control group a total of 435 PN bags were administered in 48 patients. Hence, the cost per patient was 435x €60/bag divided by 48 patients = €544/patient. In the interventional group a total of 24 parenteral nutrition infusion bags was administered in 46 patients. Conversely, the cost per patient was 24 9 €60 divided by 46 patients = €31/patient. The netto PN cost saving per patient for the hospital budget is thus €544 – €31 = €512. By reducing the median LOS with 4 days, the cost savings were 4 9 €652/day = €2,608/patient. Hence based on avoided costs, the implementation of the oral nutrition protocol was associated with a cost saving of €512 ? €2,608 = €3,120/patient.
Discussion In many centers in Europe, especially in those with governmental reimbursement for PN, PN is standard of care after RC. Our study shows that implementation of the ONP is associated with a decreased postoperative LOS as compared to systematic postoperative PN therapy. Implementation of an ONP is also associated with a reduction in administered PN infusion bags, a faster resumption of oral diet, but no difference in POCs. Furthermore, cost savings after initiating the ONP were €3,120/patient. Our data concerning LOS corroborate data from literature. On the one hand, the median baseline LOS of 18 days (IQR 15–22 days), which is the LOS in our PN group, is in line with previously reported LOS in RC patients: i.e. 21–23 days, all expressed as mean LOS [18–20]. On the other hand, in our study population, implementation of the ONP was associated with a reduction in LOS to a median of 14 [13, 18] days, as was also reported by research groups investigating enhanced recovery pathways in RC patients [5–7]. However, it is important to mention that historically LOS in Europe has always been longer than in North America. In North America, the standard use of ONP, early recovery pathways and streamlining recovery by limiting the use of parenteral medications and NGT have significantly shortened LOS. Therefore, effects on LOS may not be generalizable to North American practice. Despite POI being rather prevalent in this population, the interventional group resumed full diet significantly faster [1–7, 21]. This is explained by early initiation of the ONP and the associated stimulation of early resumption of
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Table 2 Baseline demographics
Control group (n = 48)
Interventional group (n = 46)
Males
31 (65 %)
34 (74 %)
Females
17 (35 %)
12 (26 %)
p-value
Gender
Age (y)b
66.0 (55–75)
65.5 (57–72.5)
NS (p = 0.856)
Weight (kg)a
73.7 ± 13.9
75.4 ± 14.2
NS (p = 0.563)
Length (cm)a
169.7 ± 8.2
170.8 ± 8.0
NS (p = 0.513)
BMI (kg/m2)a
25.5 ± 4.0
25.8 ± 4.3
NS (p = 0.765)
Age-adjusted Charlson comorbidity indexb
4 (3–5)
5 (3–6)
NS (p = 0.661)
Neurogenic
9 (19 %)
6 (13 %)
Oncologic
39 (81 %)
40 (87 %)
Indication for surgery
NS (p = 0.576)
Bladder cancer staging (TNM classification) Non oncologic
7 (15 %)
NS (p = 0.328) 5 (11 %)
T1N0M0
3 (6 %)
2 (4 %)
T1N ? M0
2 (4 %)
1 (2 %)
T2-3N0M0
20 (42 %)
15 (33 %)
T2-3N ? M0
8 (17 %)
10 (22 %)
T4N0M0
5 (10 %)
2 (4 %)
T4N ? M0
0 (0 %)
2 (4 %)
TisN0M0
3 (6 %)
9 (20 %)
Type of urinary diversion
NS (p = 0.359)
Ileal conduit Orthothopic neobladder
40 (83 %) 6 (13 %)
39 (85 %) 7 (15 %)
Continent cutaneous diversion
2 (4 %)
0 (0 %)
1
5 (10 %)
0 (0 %)
2
19 (40 %)
14 (30 %)
3
5 (10 %)
3 (7 %)
4
19 (40 %)
29 (63 %)
Intra-operative blood loss (ml)b
1,000 (500–1,475)
1,000 (600–1,650)
Duration of procedure (min)b
210 (180–240)
187.5 (180–240)
\0.05 (p = 0.04)
Surgeon
Baseline demographics. (NS not significant, BMI body mass index, POI postoperative ileus, NGT nasogastric tube, IQR interquartile range) a
mean
b
median
Patients with POI 39 (81 %)
33 (72 %)
Yes
9 (19 %)
13 (28 %)
2.0 (1–4.8)
2.0 (1–3)
NGT removal dayb
NS (p = 0.493) NS (p = 0.427) NS (p = 0.334)
No
full diet in the interventional group. This was confirmed by the general linear model. Improvement of nutritional care should belong to the clinical pharmacist’s portfolio as it pertains to the betterment of the individual patient’s care. As surgery is foremost uncomplicated in the majority of cases in regular RC, PN should not remain the standard of care in those patients. Switching PN to oral nutrition might enhance recovery, avoid CRBSI and PN related infections and increase
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NS (p = 0.376)
NS (p = 0.932)
comfort e.g. in terms of mobility for the patient. In our opinion, a thorough systematic evaluation instead of blind introduction of such an ONP, e.g. by initiating the protocol in two phases like we did in a before-after design, was important, as this enables to assess potential differences in complications, LOS and cost. Nevertheless, our study was subjected to potential limitations. First, the major drawback of the design of our study, i.e. a before-after study, is that it does not allow
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Table 3 Primary and secondary outcome measures
Control group (n = 48)
Interventional group (n = 46)
p-value
18 (15–22)
14 (13–18)
p \ 0.001
Primary outcome Time from surgery to dischargea (d) Secondary outcomes PN infusion bags per patient
8 (6–10)
0 (0–0)
p \ 0.001
Time to resumption of full dieta (d)
8 (6–9)
4 (3–5)
p \ 0.001
11 (23 %)
14 (30 %)
37 (77 %)
32 (70 %)
1 (1–2)
1 (0–2)
NS (p = 0.302)
4
0
NS (p = 0.117)
Control group (n = 70)
Interventional group (n = 53)
p-value
21 (30 %)
13 (25 %)
Fistula or leak
1 (1 %)
2 (4 %)
Bleeding or hematoma
5 (7 %)
2 (4 %)
13 (19 %) 13 (19 %)
16 (30 %) 4 (8 %)
Patients with POC
NS (p = 0.487)
No Yes Rate of POCs per patient
a
Patients with CRBSI POCs Type of POC Infection
Primary and secondary outcome measures. In the ‘‘POCs’’, patients with multiple complications are counted more than once. (d day, IQR interquartile range, PN parenteral nutrition, POC postoperative complications, NS not significant, CRBSI catheter related blood stream infection) a
median
Gastro-intestinal Cardiopulmonary
NS (p = 0.049)
Neurologic
0 (0 %)
5 (10 %)
Pain
2 (3 %)
0 (0 %)
Other
15 (22 %)
11 (21 %)
Severity grade of POC
NS (p = 0.698)
Grade I
15 (21 %)
16 (30 %)
Grade II
35 (50 %)
23 (44 %)
Grade III-a
16 (23 %)
12 (23 %)
Grade III-b
4 (6 %)
2 (4 %)
complete comparison for non-observed time-dependent differences between both groups. However, no change was found in type of surgery and care practices (anesthesia modalities, surgical techniques, doses of narcotics, bowel stimulants, anti-emetics and mobilization practices). Furthermore, standard of care is provided as electronic treatment schemes in our hospital, which did not change over time during our study period. In addition, evaluating the impact of the introduction of an ONP in a prospective randomized controlled manner (PRCT) is not easy to carry out. The study was conducted on two urological wards (56 beds in total), led by a team of four urologists, not assigned to a specific ward. Hence, if we would have pursued the PRCT design, results would have been biased due to knowledge on the ONP protocol by the urologists, caring for both the intervention and control patients. Moreover, the results from our post-study follow up analysis were in line with the intervention group and confirmed the associated impact on PN and LOS. Second, differences in preoperative nutrition status might have influenced outcomes. Unfortunately, no routine preoperative nutrition
status screening is performed on the urological wards. Poor preoperative nutrition status has been recognized as a major determinant for developing postoperative complications such as infections and prolonged hospital stay [6, 9, 10, 22]. However, while certainly not conclusive, we retrospectively assessed patient’s BMI values as surrogate marker for nutrition status. Four patients had a BMI \ 18.5, 2 in the control (BMI 17.51 and 17.76) and two in the intervention group (BMI 18.37 and 18.42), respectively. Based on these data we assume that the groups did not differ in terms of number of malnourished patients and that the majority was actually not malnourished at all, which is certainly an extra argument pro implementing an ONP. Third, nutritional outcomes such as daily caloric intake and biochemical markers of nutrition (serum prealbumin, albumin and total protein levels) might have added extra information. Post hoc, we were not able to assess these factors as such. However, as was shown in our follow-up group, the effect on number of infused PN infusion bags and LOS was sustained regardless of nutritional outcomes of the patients. Last, by excluding patients
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with irregular RC or with contra-indications for EN, we cannot extrapolate our results to all RC patients. On the contrary, patients with an irregular cystectomy course would have been transferred to an ICU and subjected to an alternative nutrition protocol. Furthermore, the ONP implies that the oral route is accessible immediately postsurgery, which is intrinsically not achievable in patients with preoperative contra-indications for EN. In summary, we believe that the clinically relevant results of our study are confirming that oral or enteral nutrition should be standard of care in RC patients without contra-indications. Based on our study, the ONP has become now our standard nutrition management after regular RC.
Conclusions Our study showed that an ONP, when compared to the systematic postoperative use of PN, was associated with a decreased LOS and cost in a regular RC patient population. Funding
None.
Conflicts of interest
The authors declare no conflicts of interest.
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