Implementation of an Efferent Loop Stimulation Protocol Prior to Ileostomy Closure at La Paz University Hospital
Conditions: Postoperative Ileus, Colorectal Cancer Control and Prevention, Stoma - Ileostomy
Sponsor: Hospital Universitario La Paz

 
v 5.   01/01/2025 
 
Implementation of an Efferent Loop Stimulation Protocol 
Prior to Ileostomy Closure at La Paz University Hospital. 
 
BACKGROUND AND CURRENT STATUS  
Stoma creation is a surgical procedure used in certain situations in general surgery, 
especially in colorectal and emergency surgery. There are several ways to bypass 
intestinal transit during intestinal surgery. The most frequently performed is colostomy, 
which is defined as the exteriorisation of the colon through the skin, usually on the left 
side of the abdomen. The colon can be bypassed along its entire length and a stoma can 
be created and matured in any area of the abdominal wall. In addition to the colon, in 
certain circumstances the transit can also be bypassed more proximal to the colon, such 
as the small intestine, and although any area of the intestine is susceptible to bypass, the 
most frequent is the ileum.  
The objectives of creating a stoma are diverse, and may be to prevent the passage of 
faeces to distal sections to treat an infection, to avoid a high-risk anastomosis in a patient 
with emergency surgery and haemodynamic instability, or to protect a high-risk 
anastomosis (such as rectal anastomoses due to the anatomical characteristics of their 
irrigation). Although the creation of stomas is a life-saving surgical technique, the 
bypassing of intestinal contents has both pathophysiological and aesthetic-psychological 
repercussions on patients' lives. Stomas bypass the intestinal transit and therefore cause 
food to leave the intestine before it completes its digestive transit, altering the absorption 
of nutrients. The more proximal the bypass is, the more this absorption will be altered. 
Therefore, ileostomy has more absorption problems than colostomy. This leads to a 
physiological alteration of the patient, with the more proximal the shunt is, the greater the 
loss of liquids and intestinal contents. 
The creation of ileostomies can be encountered mainly in three scenarios:  
- A surgical emergency with the need to abduct the small bowel to the skin either 
by massive colon resection or by risky anastomosis 
- Total or subtotal colectomies for various causes: inflammatory bowel diseases, 
synchronous or metachronous tumours, peritoneal carcinomatosis, etc. 
- Protective ileostomies in elective surgery for colorectal cancer or deep 
endometriosis with high-risk colorectal resection and anastomosis, either because 
of the distance to the anal margin or because of the patient's biological 
characteristics (chemotherapy, radiotherapy, immunosuppression, malnutrition). 
The latter case is the most frequent.  
TITLE: Implementation of an Efferent Loop Stimulation 
Protocol Prior to Ileostomy Closure at La Paz University 
Hospital 
PRINCIPAL RESEARCHERS:  Dr. LUIS ASENSIO GÓMEZ and Dr. 
INES RUBIO-PEREZ 
Department: CIRUGÍA GENERAL Y DEL APARATO DIGESTIVO 
i
d d
5
01/01/2025

 
v 5.   01/01/2025 
 
Stomas can be permanent or temporary. Ideally, most stomas should be temporary and 
should be used as a bridging tool to obtain the best possible conditions for the patient to 
undergo anastomosis. The literature provides us with real data that approximately 50% 
of colostomies are not reconstructed, either due to progression of oncological disease, 
clinical deterioration of the patient or unclear causes. However, given that the most 
common case of ileostomy creation is to protect an anastomosis of the intestinal transit 
to aid healing, ileostomies are reconstructed at a rate of over 90%. 
 
A second intervention is used to perform an ileostomy closure and re-establish normal 
intestinal transit. For such a closure, it is essential to choose the right time depending on 
the indications that justified the creation of the stoma and the type of stoma used. 
However, this closure is associated with a number of postoperative morbidities. The most 
frequent is postoperative ileus (POI), but there are others such as surgical wound 
infection, diarrhoea... Several studies indicate that stimulation of the efferent loop, prior 
to ileostomy closure, shows benefits in the postoperative recovery of patients. The cause 
of these complications after transit reconstruction is multifactorial and a single cause is 
unknown, but it is thought that it could be due to the colic mucosa being atrophied and 
inflamed after a variable period without stimulation, preventing the passage of intestinal 
contents, which are also nutritional for the mucosa. When previously stimulated, it seems 
that the colic trophism recovers earlier and is more prepared to receive new intestinal 
contents after intestinal reconstruction, thus decreasing the inflammation associated with 
the exclusion of food content. This means that, by stimulating the loop, it loses less of its 
properties and therefore its functionality when transit is re-established. Some of these 
benefits, translated into clinical practice, are the reduction of hospital stay and the 
reduction of post-surgical complications such as postoperative ileus, diarrhoea, 
anastomotic leaks and surgical wound infection. There is inconsistency about which 
solution to use for efferent loop stimulation. Some studies use serum and thickener, others 
use short-chain fatty acids, which are the main source of nutrition for the intestinal 
epithelial cells, and still others use probiotic substances, hoping to optimise the patient's 
intestinal microbiota.  
 
There are many doubts about the best way to do this and for how long. The time prior to 
stimulation is one of the doubts analysed by Grafinkle in a recent study, as there is a great 
deal of variability in the studies analysed. Some studies performed loop stimulation for 2 
weeks (Abrisqueta), others for 10 consecutive days (Ocaña) in a hospital setting, while 
Grafinkle et al. performed stimulation for 7 random days in the 3 weeks prior to surgery. 
None of the studies explores the difficulty of surgical planning for these patients to meet 
the timings set out in their protocols. Grafinkle et al. explores how to optimise the 
procedure by performing it fewer times, but without losing benefit in terms of outcomes. 
On this issue, several authors point to the benefit of instructing patients to perform the 
stimulation themselves, thus reducing hospital visits and thus reducing the use of health 
care resources. This could theoretically improve patient adherence by facilitating logistics 
and allowing telephone follow-up to be measured using forms. To date, despite the 
heterogeneity of study methods, probiotic stimulation has not demonstrated any 
postoperative benefit. However, there is evidence that the use of saline or short-chain 
fatty acids reduces complications such as paralytic ileus and diarrhoea. It should be borne 
in mind that the half-life of fatty acids is very short, storage is complex because it requires 
optimal temperature conditions for storage and other conditions for use, as well as their 

 
v 5.   01/01/2025 
 
high cost. In order to carry out the procedure at home, it is simpler to use serum if it has 
been demonstrated that fatty acids are not superior to serum.  
Currently, there is no protocol in place at La Paz University Hospital to perform this 
procedure, which could be of great benefit as it is a simple, cheap procedure that could 
hypothetically reduce complications and hospital stay, improving the patient's 
postoperative period and could be of economic benefit to the system. 
RATIONALE OF THE STUDY 
 
The aim of this study is to demonstrate the benefits of efferent loop stimulation prior to 
ileostomy closure for any previous cause, and to develop a practical, simple protocol that 
can be adapted to complex daily surgical planning, at the Hospital Universitario La Paz, 
in the General and Digestive System Surgery Department.  With the current evidence, we 
know that there is a real benefit of pre-stimulation, although there are scientific gaps in 
knowledge about how long to stimulate beforehand and the optimal type of substance to 
use. Furthermore, with a good organisation of the protocol, it could be possible to perform 
it at home with the aforementioned benefits.  
 
We know that complications of ileostomy closure are very frequent (estimated at around 
40%). The most frequent is postoperative paralytic ileus, but there are many others such 
as diarrhoea, anastomosis dehiscence, surgical wound infection, etc. All of these prolong 
the patient's hospital stay, increasing the use of resources that all these complications 
entail, such as possible re-interventions or the use of medication. The consequences of 
these complications for the patient involve a deterioration of their functional capacities, 
especially in fragile patients, by increasing the number of days of hospitalisation and 
complications.  Therefore, if by applying a reproducible and simple protocol of prior 
stimulation we can reduce post-surgical complications and thus hospital stay, we could 
improve the lives of these patients. 
 
 
HYPOTHESIS: Stimulation of the efferent loop (EAE) in ileostomy patients with saline 
and thickener 2 to 4 weeks prior to surgery for transit reconstruction recovers intestinal 
transit sooner, reduces hospital stay and post-surgical complications. 
 
OBJECTIVES  
 
Primary Objective 
Primary Endpoint 
To demonstrate the efficacy of efferent 
loop stimulation in reducing hospital 
stay compared to historical controls at 
30 days after reconstruction surgery. 
Difference in mean number of days of 
hospital stay between control and case 
group at 30 days after reconstructive 
surgery 
Secondary Objectives 
Secondary Endpoints 
1. To assess whether EAE reduces 
paralytic ileus 
 
2. To assess whether EAE reduces 
postoperative diarrhoea 
 
1. Percentage of patients diagnosed with 
paralytic ileus during admission in the 
case group compared to the control 
group 
 

 
v 5.   01/01/2025 
 
3. To evaluate whether SEA reduces 
surgical wound infection 
 
4. 
To 
evaluate 
the 
degree 
of 
implementation of this clinical protocol 
in the General and Digestive Surgery 
Department of Hospital La Paz 
 
5. To evaluate whether SEA reduces 
postoperative blood C-reactive protein 
values measured in the postoperative 
period  
2.Percentage of patients diagnosed with 
diarrhoea during admission in the case 
group compared to the control group. 
 
3. Percentage of patients diagnosed with 
surgical wound infection 30 days after 
surgery in the case group compared to 
the control group  
 
4. Percentage of the number of patients 
included in the protocol compared to the 
total 
number 
of 
ileostomies 
reconstructed since the protocol was 
implemented 
 
5. Percentage of the mean blood CRP 
value on the second and fourth day of 
patients undergoing EAE compared to 
the mean blood CRP value on the 
second and fourth day of patients 
without EAE. 
 
 
MATERIALS AND METHODS 
 
Inclusion Criteria: 
 
1. Subjects must be able to understand the purpose and risks of the study, giving 
informed consent and authorising the use of confidential health information.  
2. Subjects Patients over 18 years of age who, regardless of the cause, are 
ileostomy patients and have a medical indication for transit reconstruction by a 
general surgeon. 
3. Subjects able and willing to participate and to be followed up for the duration 
of the study. 
 
Exclusion Criteria 
 
1. Subjects with an ileostomy who do not wish to undergo reconstruction. 
2. Subjects who are unable to perform at least two weeks of efferent loop 
stimulation prior to reconstruction surgery. 
3. Subjects who do not consent to participate in the study. 
 
 
Study Design: Prospective Cohort Study with Historical Controls at a single centre 
 
Study Population: Patients over 18 years of age who, regardless of cause, are ileostomy 
carriers and have an indication for transit reconstruction.  
 
Intervention: 

 
v 5.   01/01/2025 
 
- Arm Cases: Prospective patients with daily stimulation of the efferent loop at 
least two weeks prior to surgery with saline and thickener. 
 
- Control Arm: Retrospective data from patients who did not undergo pre-
ileostomy closure stimulation prior to the introduction of the efferent loop 
stimulation protocol. 
 
Once the patient is included in the study, their clinical treatment will be carried out in 
accordance with standard clinical practice, to which a series of visits and procedures 
without risk to the patient will be added: 
 
1. The start of the efferent loop stimulation will be performed the day after the 
anaesthesia consultation prior to surgery to receive the information, material and 
established follow-up of the patient. 
 
2. The determination of ileostomy closure shall be recorded in the operating room 
and shall be objectified in the surgical protocol or operative sheet when 
performed. 
 
3. The patient will be reviewed daily during admission by the corresponding 
medical team, carrying out anamnesis, physical examination and serial analyses 
on days 2 and 4 with the necessary parameters for follow-up according to standard 
clinical practice. 
 
4. On-site review with anamnesis and physical examination at 1 and 6 months to 
assess the patient's general condition. 
 
Once the patient is included in the study, the management of the stimulation will be 
monitored with telephone and face-to-face follow-up once a week. 
 
During their hospital stay after ileostomy closure, their clinical management will be 
carried out in accordance with standard clinical practice, and they will be discharged from 
hospital when the established criteria are met. 
 
The criteria for discharge from hospital care are considered to be met when the patient 
meets the following 
1. Tolerance to oral diet  
2. Absence of abdominal distension  
3. Adequate pain control 
4. Absence of fever  
5.Absence of signs of surgical site infection requiring hospital care 
6. Independent mobilisation 
7.Presence of vent or stool 
 
SAMPLE SIZE 
The primary variable is defined as the difference in mean hospital length of stay between 
the control and case groups within 30 days following reconstructive surgery. Assuming a 

 
v 5.   01/01/2025 
 
mean of 5.84 days, a standard deviation of 3.04 days, a minimum detectable difference 
of 2 days, and a one-tailed hypothesis test: 
With an alpha error of 0.05 and a power of 0.8, and accounting for a potential dropout 
rate of 0.15%, a sample size of 68 patients is proposed, with 34 in each arm. 
Duration: 1 year (extendable depending on sample size requirements) 
 
STATISTICAL ANALYSIS 
A univariate descriptive analysis will be conducted for all study variables. Qualitative 
variables will be presented as absolute and relative frequencies, while quantitative 
variables will be summarised using measures of central tendency and dispersion (mean, 
standard deviation, median, interquartile range, etc.). The Kolmogorov-Smirnov test will 
be employed to assess the normality of the variables. 
For the analysis of the primary outcome and intergroup comparisons, Pearson’s Chi-
square test will be used for qualitative variables (or Fisher’s exact test for 2x2 tables and 
likelihood ratio test for m×n tables, if necessary). For quantitative variables, the Student’s 
t-test and ANOVA will be applied, or their non-parametric equivalents, the Mann-
Whitney U test and the Kruskal-Wallis test, respectively. 
Subsequently, a multivariate model will be fitted including all variables found to be 
statistically significant in the univariate analysis. The final model will be selected using 
a backward elimination approach, with optimal model determination based on the 
Bayesian Information Criterion (BIC). 
The level of statistical significance is set at 0.05. Statistical analyses will be performed 
using R software (version 4.3.1). 
ETHICAL CONSIDERATIONS 
All participants will receive detailed information regarding the study, including its 
objectives, procedures, potential risks, and benefits. Sufficient time will be provided for 
consideration, and participants will have the opportunity to ask questions prior to signing 
the informed consent (IC) form. This process ensures that consent is given voluntarily 
and is fully informed. 
Written IC, specifically designed for this study, will be obtained and signed by the patient. 
Personal and medical data will be treated with the utmost confidentiality, in accordance 
with Data Protection regulations. Data will be stored securely, accessible only to the 
research team, and anonymised to safeguard participant identity. 
Participant selection will be fair and equitable, based on clearly defined inclusion and 
exclusion criteria. Vulnerable groups will not be exploited, and equality will be promoted 
in the recruitment process. 

 
v 5.   01/01/2025 
 
Participants may withdraw from the study at any time without any negative consequences. 
They will be informed about the withdrawal procedure and the handling of their data upon 
withdrawal. 
The study has been reviewed and approved by the Research Ethics Committee of La Paz 
University Hospital, ensuring compliance with all relevant ethical and legal standards. 
Study findings will be communicated transparently and accessibly. Participants will be 
informed of the results, which will also be published in scientific journals and on publicly 
accessible platforms. 
 
RISK-BENEFIT ASSESSMENT 
This study has been designed to ensure that the potential benefits outweigh the risks. A 
risk assessment has been conducted and measures have been implemented to minimise 
them, while ensuring that the potential benefits are meaningful. 
 
CONFIDENTIALITY 
Data collected for the study will be identified using a code, and only the study physician 
or authorised collaborators will be able to link this information to the patient and their 
medical records. Therefore, individual identity will not be disclosed, except in cases of 
medical emergency or legal requirement. 
Should the data from this study be used for future research with different objectives, 
patient consent will be requested at that time, using a separate information sheet 
previously approved by the relevant Research Ethics Committee (REC). 
The processing, communication, and transfer of personal data will comply with the 
provisions of the Organic Law 15/1999 of 13 December on the Protection of Personal 
Data. In accordance with this legislation, participants may exercise their rights to access, 
rectify, oppose, or cancel their data by contacting their study physician. Data transferred 
to third parties or other countries will not include any information that could directly 
identify the participant (e.g., name, initials, address, social security number, etc.). Should 
such a transfer occur, it will be solely for the same purpose as the present study, and 
confidentiality will be safeguarded in line with current national legislation. 
Access to personal information will be restricted to the study physician, collaborators, 
authorised personnel, the Clinical Research Ethics Committee, and competent authorities 
when necessary to verify study data and procedures. Confidentiality will be maintained 
at all times in accordance with applicable laws 
 
 
REFERENCES  
 

 
v 5.   01/01/2025 
 
 
1. Garfinkle, R., Demian, M., Sabboobeh, S., Moon, J., Hulme-Moir, M., Liberman, 
A.S., Feinberg, S., Hayden, D.M., Chadi, S.A., Demyttenaere, S., Samuel, L., 
Hotakorzian, N., Quintin, L., Morin, N., Faria, J., Ghitulescu, G., Vasilevsky, C.A. 
and Boutros, M.; Bowel Stimulation Research Collaborative, 2023. Bowel 
stimulation before loop ileostomy closure to reduce postoperative ileus: a 
multicenter, single-blinded, randomized controlled trial. *Surgical Endoscopy*, 
37(5), pp.3934-3943. doi: 10.1007/s00464-022-09510-5. 
 
2. Ocaña, J., García-Pérez, J.C., Labalde-Martínez, M., Rodríguez-Velasco, G., 
Moreno, I., Vivas, A., Clemente-Esteban, I., Ballestero, A., Abadía, P., Ferrero, E., 
Fernández-Cebrián, J.M. and Die, J., 2022. Can physiological stimulation prior to 
ileostomy closure reduce postoperative ileus? A prospective multicenter pilot 
study. *Techniques in Coloproctology*, 26(8), pp.645-653. doi: 10.1007/s10151-
022-02620-1. 
 
3. Lloyd, A.J., Hardy, N.P., Jordan, P., Ryan, E.J., Whelan, M., Clancy, C., 
O'Riordan, J., Kavanagh, D.O., Neary, P. and Sahebally, S.M., 2023. Efferent limb 
stimulation prior to loop ileostomy closure: a systematic review and meta-
analysis. *Techniques in Coloproctology*, 28(1), p.15. doi: 10.1007/s10151-023-
02875-2. 
 
4. Fernández López, F., González López, J., Paz Novo, M., Ladra González, M.J. 
and Paredes Cotoré, J., 2019. Stimulation the efferent limb before loop ileostomy 
closure with short chain fatty acids. *Cirugía Española (English Edition)*, 97(1), 
pp.59-61. doi: 10.1016/j.ciresp.2018.06.018.