Does Caffeine Reduce Postoperative Bowel Paralysis After Elective Colectomy? (CaCo)

Does Caffeine Reduce Postoperative Bowel Paralysis After Elective Colectomy? - A Randomized, Placebo-controlled Trial

Postoperative bowel paralysis is common after abdominal operations, including colectomy. As a result, hospitalization may be prolonged leading to increased cost. A recent randomized controlled trial from the University of Heidelberg showed that consumption of regular black coffee after colectomy is safe and associated with a significantly faster resumption of intestinal motility (Müller 2012). The mechanism how coffee stimulates intestinal motility is unknown but caffeine seems to be the most likely stimulating agent.

Thus, this trial addresses the question: Does caffeine reduce postoperative bowel paralysis after elective laparoscopic colectomy?

Patients after laparoscopic colectomy will receive either 100 mg caffeine, 200 mg caffeine, or 250mg corn starch (placebo) 3 times daily in identically looking gelatin capsules.

The study is a randomized, controlled trial, with blinding of physicians, patients and nursing stuff (evaluating the endpoints).

Primary endpoint will be the time to first bowel movement.

Study Overview

• Status: Terminated
• Conditions: Colorectal Neoplasm; Diverticulitis; Postoperative Ileus; Laparoscopic Colectomy Without Stoma Formation
• Intervention / Treatment: Drug: Caffeine (100 mg); Other: Radiopaque marker; Drug: Caffeine (200 mg); Drug: corn starch (250 mg approx.)

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Rorschach, Switzerland, 9400
    • Department of General, Visceral, Endocrine and Transplantation Surgery, Cantonal Hospital St. Gallen
  • St. Gallen, Switzerland, 9007
    • Department of General, Visceral, Endocrine and Transplantation Surgery, Cantonal Hospital St. Gallen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients scheduled for elective laparoscopic colectomy (right or left hemicolectomy, segmental resection, extended hemicolectomy, sigmoid resection, upper rectum (anastomosis higher than 7 cm ab ano))
• There will be no upper age limit. If elderly patients are considered fit for surgery, they will be included in the study.
• Informed consent
• Application of epidural analgesia

Exclusion Criteria:

• Participation in another concurrent interventional trial
• Need for a stoma (colostomy or ileostomy) or reversal of a stoma, if the patient had a complete bowel obstruction
• Known hypersensitivity or allergy to caffeine/coffee
• Expected lack of compliance
• American Society of Anesthesiologists (ASA) Physical Status Score of IV or V
• Impaired mental state or language problems
• Alcoholism or drug abuse
• Previous extensive abdominal surgery
• Inflammatory bowel disease
• Clinically significant cardiac arrhythmia
• Cardiac insufficiency
• Pregnancy, lactation, or childbearing potential without using adequate contraception
• Intake of opioid analgesics, or steroids >5mg/d for ≥7 days before surgery
• Under anti-depressive medication
• Liver cirrhosis or compromised liver function (MELD score >15)
• Emergency procedure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Caffeine (100 mg); Verum 1 with 100 mg caffeine	Drug: Caffeine (100 mg); Patients after laparoscopic colectomy will receive 3 times daily capsules with 100 mg caffeine together with the meals. First capsule will be taken on the evening of surgery if surgery was completed before 1 pm, otherwise the first capsule will be taken on the morning of the next day. Treatment consists of 10 capsules and will be stopped after the first solid bowel movement.; Other Names: coffeinum; methyltheobromine; 1,3,7-trimethyl-3,7-dihydro-1H-purin-2,4-dion; CAS No: 56-08-2; Ph.Eur: 6.0/027; ATC code: N06BC01; Other: Radiopaque marker; On the morning of the first, second and third day after surgery patients will take 1 capsule each day with radiopaque markers . On day 4 after surgery an abdominal X-ray will be performed to localize the markers. Each gelatin capsule contains 10 markers consisting of polyurethane encapsulated barium sulfate (40%).; Other Names: Colon Transit; PZN 3351272; GTIN Code 7629999004153
Experimental: Caffeine (200 mg); Verum 2 with 200 mg caffeine	Other: Radiopaque marker; On the morning of the first, second and third day after surgery patients will take 1 capsule each day with radiopaque markers . On day 4 after surgery an abdominal X-ray will be performed to localize the markers. Each gelatin capsule contains 10 markers consisting of polyurethane encapsulated barium sulfate (40%).; Other Names: Colon Transit; PZN 3351272; GTIN Code 7629999004153; Drug: Caffeine (200 mg); Patients after laparoscopic colectomy will receive 3 times daily capsules with 200 mg caffeine together with the meals. First capsule will be taken on the evening of surgery if surgery was completed before 1 pm, otherwise the first capsule will be taken on the morning of the next day. Treatment consists of 10 capsules and will be stopped after the first solid bowel movement.; Other Names: coffeinum; methyltheobromine; 1,3,7-trimethyl-3,7-dihydro-1H-purin-2,4-dion; CAS No: 56-08-2; Ph.Eur: 6.0/027; ATC code: N06BC01
Placebo Comparator: corn starch (250 mg approx.); approx. 250 mg corn starch as placebo	Other: Radiopaque marker; On the morning of the first, second and third day after surgery patients will take 1 capsule each day with radiopaque markers . On day 4 after surgery an abdominal X-ray will be performed to localize the markers. Each gelatin capsule contains 10 markers consisting of polyurethane encapsulated barium sulfate (40%).; Other Names: Colon Transit; PZN 3351272; GTIN Code 7629999004153; Drug: corn starch (250 mg approx.); Patients after laparoscopic colectomy will receive 3 times daily capsules with 250 mg corn starch together with the meals. First capsule will be taken on the evening of surgery if surgery was completed before 1 pm, otherwise the first capsule will be taken on the morning of the next day. Treatment consists of 10 capsules and will be stopped after the first solid bowel movement.; Other Names: Amylum maydis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first bowel movement	Time from end of surgery (time of closing suture) until patient's first bowel movement (passage of stool) in hours. A patient is considered to have met the primary endpoint when he or she had first tolerated food (recovery of upper GI function) and experienced a bowel movement for the first time (recovery of lower GI function).	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first flatus	Time from end of surgery until patient's first flatus in hours. The passage of flatus will be determined by questioning the patient; the passage of a bowel movement will be determined by reference to nursing records or by the clinical judgment of the investigator or designee following questioning the patient.	7 days
Time to tolerance of solid food	Time from end of surgery until patient tolerates intake of solid food in hours. Tolerance of food is defined as the first time the patient is able to eat solid food (any food re-quiring chewing) without vomiting or significant nausea within 4 h after the meal, and without reversion to only enteral fluids.	7 days
Postoperative vomiting events	Number of times patient has to vomit.	7 days
Colonic passage time	On day 1, 2 and 3 after surgery patients take one capsule with radioopaque markers. On day 4 location and count of markers is determined by X-ray imaging and the colonic passage time is determined (Metcalf 1987).	4 days
Actual postoperative hospital stay	Number of days from surgery until actual discharge.	30 days
Theoretical postoperative hospital stay	Days from surgery until patient would be fit for release. Often patients stay longer in hospital than clinically required. Thus, evaluation of theoretical hospital stay. A patient is fit for release if: there had been bowel movement; solid food is tolerated; no serious pain; unproblematic mobilisation; surgical wound shows no sign of inflammation, or wound can be treated well in an outpatient setting; normal inflammatory markers (≤135 mg/l C-reactive protein (CRP), ≤9 10⁹/l white blood cell count)	30 days
Daily doses of analgetics	Amount, type, and time of application of analgetics will be obtained from medical and nursing records.	30 days
Postoperative pain	evaluated on the numeric rating scale (0 - 10, steps of 1)	7 days
Postoperative mobilization	Scoring: 0: 24 h in bed; 1: Out of bed only to go to bathroom; 2: Out of bed on free will	7 days
Overall fluid intake	all fluids in ml per day	7 days
Blood pressure	3 times daily	7 days
Pulse	3 times daily (or more often if required)	7 days
Intensive care	number of days in intensive care unit	14 days
Well-being	well-being evaluating on day 2 and 4 after surgery using the Basle mental state scale as well as 5 additional items to evaluate the effects of caffeine. (Hobi 1985, Hobi 1989)	4 days
Sleep behaviour	Leeds Sleep Evaluation Questionnaire (LSEQ) on day 2 and 4 after surgery. (Parrott 1986)	4 days
Sleeping habits	Questionnaire evaluating duration and deepness of sleep.	4 days
Satisfaction with surgery	Questionnaire on day 4 about satisfaction of treatment	4 days
Consumption of sleep inducing drugs	amount and type of sleep inducing drugs	7 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
preoperative caffeine consumption	Questionnaire evaluation the caffeine consumption of patients (type of beverages, amount etc)	before surgery

Collaborators and Investigators

• Sponsor: Thomas Steffen
• Collaborators: Gottfried und Julia Bangerter-Rhyner Foundation, Switzerland
• Investigators: Principal Investigator: Thomas Steffen, MD, Department of General, Visceral, Endocrine and Transplantation Surgery, Cantonal Hospital St. Gallen

Publications and helpful links

General Publications

• Parrott AC, Hindmarch I. The Leeds Sleep Evaluation Questionnaire in psychopharmacological investigations - a review. Psychopharmacology (Berl). 1980;71(2):173-9. doi: 10.1007/BF00434408.
• Muller SA, Rahbari NN, Schneider F, Warschkow R, Simon T, von Frankenberg M, Bork U, Weitz J, Schmied BM, Buchler MW. Randomized clinical trial on the effect of coffee on postoperative ileus following elective colectomy. Br J Surg. 2012 Nov;99(11):1530-8. doi: 10.1002/bjs.8885. Epub 2012 Sep 14.
• Metcalf AM, Phillips SF, Zinsmeister AR, MacCarty RL, Beart RW, Wolff BG. Simplified assessment of segmental colonic transit. Gastroenterology. 1987 Jan;92(1):40-7. doi: 10.1016/0016-5085(87)90837-7.
• Hobi V, Gerhard U, Gutzwiller F. [A report on experiences using Goldberg's GHQ (General Health Questionnaire)]. Schweiz Rundsch Med Prax. 1989 Feb 28;78(9):219-25. German.
• Hobi V. Basler Befindlichkeits-Skala. Ein Self-Rating zur Verlaufsmessung der Befindlichkeit. Manual. 1 ed. Weinheim: Beltz Test GmbH, 1985.
• Abbassi F, Muller SA, Steffen T, Schmied BM, Warschkow R, Beutner U, Tarantino I. Caffeine for intestinal transit after laparoscopic colectomy: randomized clinical trial (CaCo trial). Br J Surg. 2022 Nov 22;109(12):1216-1223. doi: 10.1093/bjs/znac265.
• Kruse C, Muller SA, Warschkow R, Luthi C, Brunner W, Marti L, Sulz MC, Schmied BM, Tarantino I, Beutner U. Does caffeine reduce postoperative bowel paralysis after elective laparoscopic colectomy? (CaCo trial): study protocol for a randomized controlled trial. Trials. 2016 Apr 4;17:186. doi: 10.1186/s13063-016-1297-1.

Helpful Links

• Web site of the Department of General, Visceral, Endocrine and Transplantation Surgery, Cantonal Hospital St. Gallen (German only)

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Actual): August 1, 2020
• Study Completion (Actual): December 22, 2020

Study Registration Dates

• First Submitted: July 27, 2015
• First Submitted That Met QC Criteria: July 27, 2015
• First Posted (Estimate): July 29, 2015

Study Record Updates

• Last Update Posted (Actual): August 4, 2021
• Last Update Submitted That Met QC Criteria: August 3, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: laparoscopy; caffeine; colectomy
• Additional Relevant MeSH Terms: Digestive System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neurologic Manifestations; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Diverticular Diseases; Colorectal Neoplasms; Paralysis; Diverticulitis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Purinergic Antagonists; Purinergic Agents; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Central Nervous System Stimulants; Caffeine
• Other Study ID Numbers: CaCo, Chir201401

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No