Epidural analgesia is associated with earlier gastrointestinal transit after radical cystectomy but does not reduce the incidence of postoperative ileus: A retrospective cohort study

Introduction

The main complications in the first 30 days after radical cystectomy (RC) are of gastrointestinal origin.^1,2 Increased sympathetic tone caused by pain, the use of systemic opioid analgetics and neuroinflammatory processes in the intestine all contribute to postoperative intestinal hypomotility.^3–5 Complications range from nausea, over paralytic postoperative ileus (POI) to complete bowel obstruction. These pathologies may promote anastomotic leakage in the gastrointestinal tract requiring further surgical intervention.

Therefore, the quick return of gastrointestinal passage after an RC is a critical goal. Delayed gastrointestinal passage in the sense of a paralytic ileus increases mortality and morbidity of the patient and should therefore be avoided.^6,7 In clinical studies, the time until the first flatus or until the first defecation is often chosen as a parameter to assess recovery after surgery, ⁸ but there is no common definition of what a postoperative paralytic ileus is. ⁹

Analgesia may either be ensured by the use of systemic opioids or by a combination of general and epidural anaesthesia. The optimal anaesthesia technique is still being discussed. On one hand, the advantages of epidural anaesthesia are reduced postoperative pain and a lower rate of cardiac and pulmonary complications. ¹⁰ On the other hand, the need for vasopressors and intraoperative fluid intake is increased to counteract the hypotension induced by the sympatholytic effect of the epidural analgesia. This may contribute to a higher incidence of intestinal anastomosis insufficiency by increasing suture edema.^11,12

In major abdominal surgery, the use of epidural analgesia with local anaesthetics has been shown to accelerate the return of gastrointestinal transit without increasing the incidence of anastomotic leakage or prolonging the length of hospital stay. ¹³ This effect seems to depend on a direct blockade of the inhibitory sympathetic intestinal innervation, a reduction of pain, and thus a reduction of intra- and postoperative opiate demand and a direct systemic effect of the administered local anaesthesia.^14,15

However, the evidence is not as distinct for RC. While some authors report no benefit for gastrointestinal dysfunction when using epidural anaesthesia, ¹⁶ others appraise improved bowel function. ¹⁷ The aim of this study was to evaluate the effect of combined epidural thoracic analgesia and general anaesthesia (CEGA) in RC with respect to the return of gastrointestinal passage, the incidence of paralytic POI, the incidence of anastomotic leakage and the length of hospital stay compared to general anaesthesia (GA) only.

Methods

This retrospective cohort study was approved by the local Ethics Committee, University of Freiburg, Germany (approval no. EK 352/18). The study was conducted at the Department of Anesthesiology and Critical Care, Medical Center – University of Freiburg, Faculty of Medicine – University of Freiburg, Germany.

The study was planned and designed in accordance with the initiative for Strengthening the Reporting of Observational Studies in Epidemiology (STROBE), using the suggested checklist for epidemiological cohort studies. The study was initiated and designed in 2018; the retrospective data collection was conducted in 2018/2019. Due to the start of an electronical patient data and management system in July 2011, which enables complete clinical data acquisition, we only included files of July 2011 or later. As we included only closed files and the data collection started in October 2018, cases after 30 September 2018 were not included. Inclusion criteria for this study were patients with bladder cancer undergoing RC between July 2011 and September 2018 at the Medical Center – University of Freiburg. Exclusion criteria included a sufficient lack of variables recorded in the patient records and registries and an age of under 18 years (Figure 1).

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Figure 1.

Flow chart of data and case selection.

The study cohort consists of all consecutive RCs between July 2011 and September 2018 at the Medical Center – University of Freiburg. The sample size is the result of including all RCs from July 2011 until September 2018. We used the convenience sampling method; therefore, a priori sample size was not calculated.

Patients with epidural analgesia were visited daily to check for adjustment of analgesia or associated complications. Prior to surgery, 8–10 mL ropivacaine 0.2% and 25 µg Sufentanil were administered via the epidural catheter. On the surgical ward, ropivacaine 0.2% 4–12 mL/h was applied continuously for the first 5–9 days through the epidural catheter. Direct postoperative treatment was performed in the intensive care unit and then continued on the surgical ward.

The data were collected from anaesthesia records, intensive care unit and regular patient records as well as the Comprehensive Cancer Center Freiburg (CCCF) cancer registry. We collected epidemiological data such as age and gender of patients, information on perioperative fluid management, anaesthesia management, comorbidities and cancer-specific data. The definition of the European Perioperative Clinical Outcome (EPCO), which defines a paralytic ileus as the intolerance of solid food or no bowel movements for 3 or more days after surgery, was applied. ¹⁸ The data were collected in a data sheet in MS Excel (Microsoft, Redmond, CA, USA).

Comparisons between individual characteristics were done for those who did/did not receive a thoracic epidural anaesthesia. Statistical analyses of continuous variables were calculated using the two-tail Student’s t-test and χ² test for categorical variables with a significance level of p < 0.05, respectively. In the cohort, multivariable binary logistic regression analysis was employed to assess the impact of baseline characteristics and epidural anaesthesia on delayed gastrointestinal function. Prior to multivariable binary logistic regression analysis, the baseline characteristics were identified by univariate analysis of delayed gastrointestinal function risk factors, which were then evaluated in a multivariable logistic regression model using all available characteristics.

Results

The study sample included 236 consecutive patients who underwent RC. A CEGA was administered to 202 patients, while 34 patients received only GA. The descriptive statistical data of the patients are presented in Table 1.

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Table 1.

Patient characteristics.

	CEGA, N = 202	GA, N = 34	p-value
Age mean (years)	67.9	67.7	0.934
Male sex (n (%))	151 (75%)	24 (73%)	0.805
Body mass index (kg/m2)	26.4	27.1	0.382
Diabetes (n (%))	33 (17%)	3 (11%)	0.525
Coronary heart disease (n (%))	39 (20%)	10 (30%)	0.159
Pulmonary disease (n (%))	30 (15%)	4 (12%)	0.672
Hypertension (n (%))	122 (61%)	26 (81%)	0.027
Preoperative anaemia (n (%))	71 (35%)	14 (42%)	0.421
ASA 3/4 (n (%))	88 (44%)	19 (58%)	0.135
T3/T4 (n (%))	104 (54%)	12 (36%)	0.063
N0 (n (%))	123 (61%)	21 (64%)	0.765
Crystalloid fluid intraoperative (L)	5.3	4.8	0.147
Colloid fluid intraoperative (mL)	201	182	0.763
Blood loss intraoperative (mL)	608	818	0.187
Maximum noradrenaline intraoperative (µg/kg/min)	0.13	0.13	0.988
Volume inflow first 24 hours (L)	5.1	4.2	0.005
Diuresis first 24 hours (L)	2.0	2.2	0.338
Maximal first 24 hours (µg/kg/min)	0.046	0.019	0.002
Postoperative paralytic ileus (n (%))	68 (34%)	14 (42%)	0.329
Anastomotic leak (n (%))	17 (8%)	4 (12%)	0.490
Revision needed first 90 days (n (%))	35 (17%)	3 (9%)	0.231
Pulmonary complications (n (%))	23 (11%)	2 (6%)	0.359
Cardiovascular complications (n (%))	13 (6.4%)	3 (9.1%)	0.580
ICU stay (days)	3.72	3.88	0.862
Hospital stay (days)	17.97	19.25	0.597
Day of first defecation (days)	2.64	3.27	0.011

CEGA: combined epidural thoracic analgesia and general anaesthesia; GA: general anaesthesia; ICU: intensive care unit; ASA: American Society of Anaesthesiologists.

The baseline characteristics of patients with and without CEGA show no significant differences in age, body mass index (BMI), gender, American Society of Anaesthesiologists (ASA) score and pathological end stage after RC.

Intraoperative treatment reveals no significant difference between the duration of the procedure, blood loss, need for vasopressors, or volume intake. However, in the first 24 hours after surgery, patients with CEGA required an increased amount of vasopressors and volume intake compared to patients with GA only.

In the first 90 days after surgery, 82 (34.7%) patients had a POI. Twenty-one (8.9%) developed anastomotic leakage in the gastrointestinal tract and a total of 38 (16%) patients needed revision in the first 90 days after RC. Twenty-five (11%) patients had pulmonary complications and 16 (7%) had cardiovascular complications. There was no significant difference between complications in the CEGA and GA groups.

Patients with CEGA showed a significant increase in gastrointestinal passage (Figure 2). The time to first bowel movement was 2.64 (standard deviation (SD) = 1.36 days) days in the CEGA group and 3.27 (SD = 1.15 days) in the GA group.

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Figure 2.

Patients with spontaneous bowel movement after radical cystectomy.

A multivariable binary logistic regression analysis with defecation after POD 3 as dependent variable identifying independent risk variables showed that not having a CEGA increased the probability of delayed bowel movement and showed an odds ratio of 3.10 (95% confidence interval) (Table 2). There was no difference in mean hospital stay between the CEGA group (17.75 days (SD = 10.90 days)) and the GA group (18.82 days (SD = 20.31 days)).

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Table 2.

Multivariate binary regression analysis to identify independent risk variables for delayed bowel movement.

	OR (95% CI)	p
No CEGA	3.018	0.017
Age (1 year)	1.031	0.031

OR: odds ratio; CI: confidence interval; CEGA: combined epidural thoracic analgesia and general anaesthesia.

Discussion

Postoperative disturbances of the gastrointestinal function are among the most common and significant side effects of abdominal surgery. ⁴ While symptoms usually start from simple discomforts such as nausea, vomiting and a distended abdomen, the disturbed gastrointestinal function may lead to more critical complications such as surgical site infections or anastomotic leaks. ¹⁹ In this study, the use of a thoracic epidural analgesia decreased the time to first bowel movement by 12.9 hours. Despite numerous advances in recent years in the surgical and perioperative environment to accelerate recovery after abdominal surgery, delayed gastrointestinal passage still continues to affect a large proportion of patients. Especially in the elderly and multimorbid population of patients with muscle invasive bladder carcinoma, this complication is very common. Reducing the risk of gastrointestinal complications should be the primary goal of any enhanced recovery strategy.

The results of this study show that the return of gastrointestinal function is significantly faster in patients with thoracic epidural anaesthesia. Although this effect is strong in the first 72 hours after surgery, it balances out after this time. The rate of POI in this study (34.7%) is very high compared to previously reported series. ⁹ Due to the lack of a uniform definition and the incidence of POIs, which are often observer-dependent, a comparison of these figures is difficult. In this study, we used the definition of the European Perioperative Clinical Outcome (EPCO) standards, according to which a paralytic ileus is defined as the failure to tolerate solid food or defecate for 3 or more days after surgery. ¹⁸ This is earlier than most definitions of POI and may explain our high rate of POI. Although we saw a trend towards a reduction of POI in patients with CEGA, it was not significant.

Negative effects of CEGA are the increased risk of hypotension due to induced vasoplegia.^12,20 This effect may increase the need for vasopressors and fluid in the perioperative episode. Also the use of epidural analgesia has also been found to influence the anastomotic blood flow after colorectal and oesophageal surgery.^21,22

While there was no significant increase in vasopressor consumption or fluid intake during surgery in this study, the postoperative fluid intake was increased as well as the need for vasopressor therapy in the first 24 hours after surgery. However, the additional fluid intake did not appear to increase the risk of anastomotic leakage in the gastrointestinal tract or lead to cardiopulmonary complications due to fluid overload. In the cohort of this study, there was no difference in duration of hospital stay when compared GA and CEGA.

This study has several limitations. First, due to the retrospective and non-randomised design, we could not provide definitive scientific evidence that the use of epidural anaesthesia increases gastrointestinal passage. An unknown or unobserved variable could lead to the difference in gastrointestinal passage in the two groups. Furthermore, we have observed only a relatively small group of patients GA only. Obviously further and more detailed studies using prospective and randomised designs are needed to clarify the effect of CEGA on gastrointestinal function and the incidence of POIs.

Conclusion

This study in a cohort of 236 patients shows that thoracic epidural analgesia accelerates the return of gastrointestinal passage in patients following RC by 12.9 hours. Despite an increased fluid intake and need for vasopressors in the postoperative period, it did not appear to increase the risk of anastomotic leakage in the gastrointestinal tract or lead to prolonged hospital stay. We did not see a significant decrease of POI in patients with CEGA, but we believe that the faster return of gastrointestinal function is still a benefit for these patients especially since we could not find any negative effects for the CEGA on patient outcome.