Facilitating early recovery of bowel motility after colorectal surgery: A systematic review

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1 See discussions, stats, and author profiles for this publication at: Facilitating early recovery of bowel motility after colorectal surgery: A systematic review Article in Journal of Clinical Nursing June Impact Factor:. DOI: 0./jocn. Source: PubMed CITATIONS READS authors: Asa Wallström University Hospital Linköping PUBLICATION CITATIONS Gunilla Hollman Frisman Linköping University PUBLICATIONS 0 CITATIONS SEE PROFILE SEE PROFILE All in-text references underlined in blue are linked to publications on ResearchGate, letting you access and read them immediately. Available from: Gunilla Hollman Frisman Retrieved on: 0 May

2 J O C N B Dispatch:.. Journal: JOCN CE: Raja S. Journal Name Manuscript No. Author Received: No. of pages: PE: Mohanapriya 0 ; REVIEW Facilitating early recovery of bowel motility after colorectal surgery: a systematic review Åsa Wallström and Gunilla H Frisman Aims and objectives. To determine how restored gastrointestinal motility can be accelerated after colorectal surgery. Background. Regaining normal bowel functions after surgery is described as unexpectedly problematic. Postoperative ileus is expected after all surgery where the peritoneum is entered, and the length of surgery has little or no impact in terms of the duration of Postoperative ileus. There is some speculation about the best way to facilitate bowel motility after colorectal surgery. Design. A systematic review. Method. The computerised databases Medline, Scopus and CINAHL were searched to locate randomised, controlled trials by using the following keywords: colorectal surgery, postoperative ileus, recovery of function and gastrointestinal motility. The systematic search was limited to studies published between January 0 January. Reference lists were also searched manually. Results. A total of randomised, controlled trials were included in the review. Recovery of gastrointestinal motility was accelerated when one of the following forms of treatment was administered: probiotics, early feeding in combination with multimodal regimes, pentoxifylline, flurbiprofen, valdecoxib, ketorolac, clonidine, ropivacaine, lidocaine or spinal analgesia. Gum chewing, preoperative carbohydrate loading, bisacodyl and Doppler-guided fluid management have an uncertain effect on bowel motility. The use of non-pharmacological interventions, intrathecal morphine, restricted fluid therapy and choline citrate yielded no significant acceleration in bowel motility. Conclusions. A multimodal treatment, where the use of morphine is restricted, seems to be the best way to accelerate the recovery of gastrointestinal bowel motility. However, more studies are required to optimise the multimodal protocol. Relevance to clinical practice. The early return of bowel functions leads to quicker overall postoperative recovery, which may ease patient discomfort and decrease hospitalisation costs. Key words: colorectal surgery, enhanced recovery, gastrointestinal motility, multimodal treatment, postoperative care Accepted for publication: January Introduction Postoperative recovery is a dynamic process during which patients try to regain their independence and return to everyday life. Their ability to return to normal living involves a conscious act, whereas regaining control of physical functions is considered to be beyond the individual s control (Allvin et al. 0). Authors: Åsa Wallström, RN, MScN,????, Department of Surgery, Östergötland County Council, Linköping; Gunilla H Frisman, RN, Associate Professor, Division of Nursing, Department of Medicine and Health, Faculty of Health Science, Linköping and Anaesthetics, Operations and Speciality Surgery Centre, Östergötland County Council, Linköping, Sweden The stomach and jejunum normally regain regular motility hours after major surgery, while this takes hours in the colon (Waldhausen et al. 0, Condon et al. ). Regaining normal bowel functions after surgery is described as unexpectedly problematic (Allvin et al. 0). During early postoperative recovery, patients preoccupation with bowel activity can contribute to a fear of pain and make them worry about bed soiling (Worster & Holmes 0). Correspondence: Åsa Wallström, Department of Surgery, Östergötland County Council, Linköping, Sweden. Telephone: asa.wallstrom@lio.se Blackwell Publishing Ltd Journal of Clinical Nursing, doi: 0./jocn.

3 Å Wallström and GH Frisman 0 Postoperative ileus (POI) is defined as a transient cessation of coordinated bowel motility after surgical intervention, which prevents effective transit of intestinal contents or tolerance of oral intake (Delaney et al. 0). POI is to be expected after surgery, especially if the peritoneum is entered, and bowel resections have the highest incidence of POI compared with other common abdominal-related surgery. The incidence of POI following large bowel resections is %, based on a total of, annual projected procedures in the USA (Goldstein et al. 0). Symptoms of POI are abdominal distension, nausea, vomiting, stomach cramps and absence of bowel sounds. One explanation for the symptoms is that there is a delayed recovery of motility patterns in combination with bowel contractions. As a consequence, no flatus or stool is passed per rectum (Morson et al. 0, Holte & Kehlet 00). The aetiology of POI is multifactorial, but can broadly be divided into factors related to surgical procedure and factors related to pharmacological interventions. These include the activation of inhibitory reflexes, inflammatory mediators and opioids (Livingston & Passaro 0, Delaney et al. 0). The first few days after colorectal surgery are stressful for the patients, both physically and psychologically. Physical symptoms such as nausea and bowel motility dysfunction are often associated with fear and anxiety about complications (Allvin et al. 0, Jonsson et al. ). To prevent fear and anxiety in the postoperative phase, patients need information about their role in postoperative recovery (Fearon et al. 0, Lassen et al. 0). Avoiding postoperative nausea and vomiting is essential from the patient s perspective (Habib & Gan 0, Kerger et al. 0). One way to relieve postoperative nausea is to create a nursing care situation where the patients are well informed and assisted in taking control over their own situation. Nurses may assist patients in taking control by being informative, available and understanding, thereby making the postoperative recovery less frightening and more manageable (Börjeson et al. 0). The duration of POI is defined as the time from surgical intervention until passage of flatus or stool, and until initiation of adequate oral intake that is tolerated and maintains hydration during hours (Delaney et al. 0). The length of surgery has little or no impact in terms of the duration of POI (Wilson, Livingston & Passaro 0). However, patients discomfort and the length of their stay in hospital can be decreased using minimal invasive techniques (Mattei & Rombeau 0). Moreover, if the surgeon has had specialised surgical training, this has been shown to shorten the duration of POI after elective colectomy. Surgical training should therefore be considered an important factor in minimising the duration of POI (Gervaz et al. 0). Where POI lasts longer than six days, it is defined as abnormally prolonged ileus. Intraoperative blood loss and postoperative opiate medication have been identified as risk factors for prolonged POI (Artinyan et al. 0). Postoperative ileus leads to pain, increased catabolism, decreased ambulation and patient discomfort. Surgical patients with POI also have a higher risk of pulmonary complications (Kehlet 00), and the economic side effects of POI are not insignificant. POI after colectomy leads to extended hospital stays and % increased hospitalisation costs (Iyer et al. 0). According to Goldstein et al. (0), the median length of hospital stay among colectomy patients with POI was four days longer than for colectomy patients with a normal postoperative recovery. A survey was conducted in the USA and in five European countries to investigate clinical practice in colonic surgery. The survey showed that perioperative care did not conform to published clinical guidelines, as postoperative nasogastric tubes were left in many patients for several days, and % of the patients did not eat solid food before day or after the operation (Kehlet et al. 0). According to Holte and Kehlet (0), the duration of POI can be reduced to days after colonic surgery with a multimodality treatment programme. However, where standardised accelerated postoperative care programmes are used for bowel surgery patients, the reported incidence of POI is still relatively high. In a study by Wolff et al. (0), POI was reported in % of patients who had had bowel resections followed by enhanced recovery pathway care. The findings indicate that improvements are required to ameliorate postoperative recovery. Aims and methods The aim of this systematic review was to determine how restored gastrointestinal motility can be accelerated after colorectal surgery. A systematic literature search was conducted in the computerised databases Medline, Scopus and CINAHL to locate randomised controlled trials (RCTs). RCTs produce the highest levels of evidence and are recognised as the gold standard of systematic reviews (Roe 0, Cochrane Consumer Network 0). Randomised controlled trials were eligible for inclusion if they were () published between January 0 January, () published in English, () based on research from adult humans (men and women > years), () refereed and () focused on ways of Blackwell Publishing Ltd Journal of Clinical Nursing

4 Review Facilitating early recovery of bowel motility after colorectal surgery 0 accelerating gastrointestinal motility after colorectal surgery. Gastrointestinal motility was evaluated in the review by using the following outcome measures: passage of flatus, defecation and bowel movement. Randomised controlled trials were excluded if the findings () involved the surgical technique or method or () lacked information about when postoperative gastrointestinal motility was first observed. The studies were identified using mainly medical subject headings (MeSH). The following search terms were used: colorectal surgery, postoperative ileus, recovery of function and gastrointestinal motility. The search was conducted by the first author, using combined keywords. Boolean operators (AND, OR) were used to expand or limit the search. Individual search strategies were used for each database because of their unique indexing terms. The Medline and CINAHL databases were searched for RCTs, English language, adult and human, as well as by publication date. Scopus was only searched by publication date and English language, as it was not possible to search by RCT, adult or human. Reference lists of cited articles were searched manually, and three leading researchers in the area of colorectal surgery were contacted to identify additional studies, in an attempt to reduce publication bias (Roe 0). The first author examined all the abstracts from the electronic database search and the manual search. All the studies involved were checked in Ulrichsweb to confirm that they had been peer-reviewed. A protocol (Table ) was used to facilitate quality assessment (Roe 0), and two reviewers undertook an independent quality assessment of the studies involved. Any disagreement between the reviewers was resolved through discussion and by referring to the original protocol Table Questions extracted from the quality assessment protocol reproduced by Roe (0) Is the study relevant to the review? Is the study a randomised or quasi-randomised trial? Was there a clear description of inclusion and exclusion criteria? Was there potential for selection bias at trial entry (quality of concealment)? Were participants blind to treatment status? Were healthcare providers blind to treatment status? Were outcome assessors blind to treatment status? Were the groups treated identically, other than for named interventions? Was there a description of withdrawals, dropouts and those lost to follow-up? Are results reported for trial? Are participants analysed in the groups they were originally allocated to? developed by Grant et al. 0,. All studies were assessed according to a strict definition of intention to treat, where all randomised patients had to be analysed (Gunnarsson 0). Data were extracted independently by one reviewer for each individual study and checked by a second reviewer. Disagreement between the reviewers was resolved through discussion, until consensus was reached. Results A total of studies were identified through electronic databases (Scopus 0, Medline, CINAHL ), and studies were found as a result of a manual search (Fig. ). One of three of the leading researchers replied after they had been contacted, but they had no knowledge of any unpublished studies on the subject. Twenty-five studies were identified as duplicates and thus removed. The most common reasons for excluding abstracts were () failure to meet the study design criteria or () failure to deal with methods of accelerating gastrointestinal motility after colorectal surgery. In total, studies were retained for full-text analysis, after which eight more studies were excluded as they failed to meet the inclusion criteria (Table ). This left studies for analysis. The studies that remained had involved a total of participants, which provided a mean sample size of participants. The extracted data are presented (Table ) through a synthesis of the results of the studies analysed. The interventions in this review differed widely. Comparisons were made using nutritional treatment, fluid therapy, laxatives, multimodal treatment, methods to decrease the use of opioids, other pharmacological treatment and non-pharmacological interventions, which revealed a number of influences on how gastrointestinal bowel motility is restored Nutritional treatment 0 Nutrition The effect of nutrition prior to surgery was analysed in two studies (n = ) (Noblett et al. 0b, Liu et al. ). One study (n = 00) (Liu et al. ) was double-blinded and placebo-controlled, while the other study mentioned blinding of healthcare staff but lacked a description. Time to first defecation was significantly reduced with probiotics (Liu et al. ). However, there was no evidence of a reduction in length of hospital stay. Compared with standard treatment, time to first passage of flatus and length of hospital stay were not reduced with preoperative carbohydrate loading, although there was evidence of a trend towards this (Noblett et al. 0b). Blackwell Publishing Ltd Journal of Clinical Nursing

5 Å Wallström and GH Frisman 0 Figure Flowchart. Identification Screening Eligibility Included Studies identified by searching the databases Medline (), Scopus (0), CINAHL () (n = ) Table Articles excluded after full-text analysis, giving the principal reason for exclusion (Delaney et al. 0) (Gatt et al. 0) (Han-Geurts et al. 0) (Lloyd et al. 0) (Nisanevich et al. 0) (Serclova et al. 0) (Suehiro et al. 0) (Zingg et al. 0) Colorectal surgery not analysed separately No outcome measures for bowel motility Colorectal surgery not analysed separately Not randomised Colorectal surgery not analysed separately Colorectal surgery not analysed separately Not randomised Subgroup study based on trial Early feeding Postoperative early feeding versus standard care was investigated in two studies (n = ) (Feo et al. 0, da Fonseca et al. ). In one study (n = 00) (Feo et al. 0), the fasting group had nasogastric tubes until first passage of flatus. The results did not show any significant differences in terms of time to first bowel movement or length of hospital stay. In the second study (da Fonseca et al. ), where the (McCormick et al. 0) participants in both groups followed a simplified rehabilitation programme, the results showed significantly shorter Studies identified by a manual search (n = ) Studies after duplicates removed (n = ) Abstract screened (n = ) Full-text studies assessed for eligibility (n = ) Studies included in the systematic review (n = ) Additional studies identified after contact with leading researchers (n = 0) Studies excluded (n = ) Full-text studies excluded (n = ) Not only colorectal surgery n = Not randomised n = No measures of bowel motility n = Subgroup study based on trial n = time to first bowel movement and a reduced stay in hospital. The three studies were assessed and shown to be comparative. Gum chewing Gum chewing as an intervention for accelerating the restoration of gastrointestinal bowel motility was investigated in six studies (n = ) (Asao et al. 0, McCormick et al. 0, Hirayama et al. 0, Matros et al. 0, Quah et al. 0, Schuster et al. 0). Four of these studies (n = ) (Asao et al. 0, McCormick et al. 0, Hirayama et al. 0, Schuster et al. 0) were very brief and gave poor descriptions of methods and results. The lack of information made it difficult to evaluate whether the groups had been treated identically other than for named interventions (McCormick et al. 0, Schuster et al. 0). Time to first passage of flatus was significantly reduced in two of the studies (n = ) (Asao et al. 0, Hirayama et al. 0). Bowel movement occurred earlier in two of the studies (n = ) (McCormick et al. 0, Schuster et al. 0), while time to first defecation was shorter in two other studies (Asao et al. 0, Hirayama et al. 0). Two of the studies provided evidence of reduced length of hospital stay (McCormick et al. 0, Schuster et al. 0). The two studies (Matros et al. 0, Quah et al. 0) with the best quality assessment of the six showed no significant differences between the groups. Blackwell Publishing Ltd Journal of Clinical Nursing

6 Review Facilitating early recovery of bowel motility after colorectal surgery 0 Table Randomised studies promoting postoperative gastrointestinal motility Study Method Participants Intervention Outcomes Limitations/Notes Withdrawals not mentioned Time to first flatus and time to first defecation were shorter in the intervention group (p < 00). The reduction in LOS was not significant () Gum chewing (n = 0). Chewed gum three times a day, from POD one until oral intake. () Control (n = ). No gum chewing Patients (n = ) with colorectal cancer undergoing laparoscopic colectomy. Inclusion or exclusion criteria not stated -arm RCT. Mentions random allocation, but no description given Asao et al. (0) trial. Powered Time to first defecation and LOS were shorter in the intervention group (p = 00). There was no significant difference terms of time to first flatus () Ropivacaine (n = ). A continuous wound infusion with ropivacaine was started when the wound was closed. () Control (n = ). Received a continuous 0% saline infusion Patients (n = ) undergoing elective open resection of colorectal tumours. and exclusion criteria. Participants excluded after randomisation (n = ) -arm RCT. Adequate concealment. Double-blinded. Placebo-controlled Beaussier et al. (0) trial. Powered No significant difference terms of time to first flatus or LOS (). Morphine (n = ). Received preoperative intrathecal morphine, injected via the L L interspace. (). Control (n = ). Received preoperative placebo saline, injected in the subcutaneous space at the L L level Patients (n = ) >0 years old undergoing resection of left colon or rectum due to cancer. and exclusion criteria. Patients excluded after randomisation (n = ) -arm RCT. Adequate concealment. Double-blinded. Placebo-controlled Beaussier et al. (0) trial Time to first bowel movements (p < 000) and time to first flatus (p = 00) were shorter in the intervention group () Morphine + ketorolac (n = ). Received morphine and ketorolac postoperatively in a PCA device. () Control (n = ). Received morphine postoperatively in a PCA device Patients (n = 0) undergoing elective colorectal resections. and exclusion criteria. Participants excluded after randomisation (n = ) -arm RCT. Adequate concealment. Double-blinded Chen et al. (0) Blackwell Publishing Ltd Journal of Clinical Nursing

7 Å Wallström and GH Frisman 0 Table (Continued) Study Method Participants Intervention Outcomes Limitations/Notes trial. Unclear whether the groups were treated identically Time to first bowel movement was shorter (p < 00) in the ketorolac group. No significant difference terms of LOS or time to first flatus () Ketorolac (n = ). Received a PCA device with morphine and ketorolac. () Morphine (n = ). Received a PCA device with morphine Patients (n = ) undergoing elective colorectal resections. Clear description of inclusion and exclusion criteria. Participants excluded after randomisation (n = ) -arm RCT. Adequate concealment. Double-blinded Chen et al. (0) trial. Underpowered. MBP prior to laparoscopic surgery Time to first flatus (p = 00) and LOS (p = 0000) were shorter in the intervention group () Early feeding (n = ). Oral liquid diet on POD and a regular diet within the next hours. () Traditional care (n = ). Nothing by mouth until the first flatus. Oral liquid diet and a regular diet within the next hours Patients (n = ) undergoing colorectal surgery. and exclusion criteria. Participants excluded after randomisation (n = ) -arm RCT. Adequate concealment da Fonseca et al. () Powered No significant differences terms of LOS or time to first bowel movement () Received a nasogastric tube and were not allowed to eat or drink before passage of flatus (n = ). () Were allowed to drink POD and to eat a soft diet POD (n = ) Patients (n = 00) undergoing elective colorectal resection for cancer. Clear description of inclusion and exclusion criteria -arm RCT. Adequate concealment Feo et al. (0) trial. Underpowered. MBP No significant differences terms of time to first flatus and bowel movement, or in terms of LOS () Relaxation (n = ). Listened to a tape with instructions, with the aim of encouraging relaxation. () Guided imagery (n = ). Listened to a tape with instructions, with the aim of calming and activating inner resources. () Control (n = ). Standard care Patients (n = ) undergoing elective conventional resection of a primary colorectal carcinoma. and exclusion criteria. Patients excluded after randomisation (n = ) -arm RCT. Age-stratified. Adequate concealment. Blinded Haase et al. (0) Blackwell Publishing Ltd Journal of Clinical Nursing

8 Review Facilitating early recovery of bowel motility after colorectal surgery 0 Table (Continued) Study Method Participants Intervention Outcomes Limitations/Notes trial. Significant preexisting hypertension in the lidocaine group. Powered LOS (p = 000), time to first bowel movement, time to first flatus and time to first defecation were shorter (p < 00) in the intervention group () Lidocaine (n = ). Received lidocaine I.V. as a loading dose before anaesthesia. A continuous lidocaine infusion started after intubation and stopped hours after skin closure. () Control (n = ). Received NaCl 0% intravenously Patients (n = ) undergoing elective colorectal surgery. Clear description of inclusion and exclusion criteria. Participants excluded after randomisation (n = ) -arm RCT. Adequate concealment. Double-blinded. Placebo-controlled Herroeder et al. (0) trial. Postoperative randomisation. Participants not analysed in the groups they were originally allocated to. MBP prior to left-sided resections No significant differences terms of LOS, or time to first flatus or first defecation () Choline citrate (n = ). Received choline citrate injections every hours until defecation or a maximum of 0 injections. () Placebo (n = ). Received sodium chloride Patients (n = ) with Postoperative ileus hours after elective open/laparoscopic colorectal resection. Clear inclusion and exclusion criteria. Patients excluded after randomisation (n = ) -arm RCT. Mentions random allocation but no description given. Double-blinded. Placebo-controlled Herzog et al. () Brief description of methods. Withdrawals not mentioned Time to first flatus (p = 000) and time to first defecation (p = 00) were shorter in the intervention group () Gum chewing (n = 0). Received three pieces of gum a day. Each piece of gum was chewed for about minutes. each mealtime. () Control (n = ). No gum chewing Patients (n = ) undergoing elective open surgery due to colorectal cancer. Unclear description of inclusion and exclusion criteria -arm RCT. Mentions but no description given Hirayama et al. (0) trial. All patients in the trial > years. Powered No significant differences time to first flatus, bowel movements or defecation () Restricted fluid (n = ). No fluid preload at placement of epidural. Restricted fluid during surgery. No I.V. fluids postsurgery. () Liberal fluid (n = ). Fluid preload at placement of epidural. Liberal fluid during surgery. I.V. fluids postsurgery Patients (n = ) undergoing elective colonic surgery. Clear description of inclusion and exclusion criteria. Participants excluded after randomisation (n = ) -arm RCT. Adequate concealment. Double-blinded Holte et al. (0) Blackwell Publishing Ltd Journal of Clinical Nursing

9 Å Wallström and GH Frisman 0 Table (Continued) Study Method Participants Intervention Outcomes Limitations/Notes Powered. MBP in the control group Time to first restoration of bowel function (p = 00) and LOS (p = 000) were shorter in the intervention group () Fast track (n = ). Followed a fast-track protocol. () Control (n = ). Conventional care programme Patients (n = ) undergoing elective open colorectal surgery for neoplasm. Clear description of inclusion and exclusion criteria -arm RCT. Adequate concealment Ionescu et al. (0) trial. Underpowered. MBP Time to first defecation and LOS were shorter (p < 000) in the multimodal arm () Multimodal (n = ). Pre- and intraoperative I.V. fluid restriction, removal of nasogastric tube on POD 0, thoracic epidural and postoperative mobilisation on POD 0. No diet restriction. () Control (n = ). Intravenous fluids given preoperatively. Normal intraoperative fluid practice. Removal of nasogastric tubes POD. No diet allowed until signs of bowel recovery. Mobilisation on POD Patients (n = ) with colorectal cancer undergoing colorectal surgery. Clear description of inclusion and exclusion criteria. Participants excluded after randomisation (n = ) -arm RCT. Adequate concealment Khoo et al. (0) trial. Powered. MBP prior to left-sided resection Bowel functions returned earlier after spinal analgesia (p = 00) than following epidural analgesia. The difference between PCA and epidural was not significant. LOS was shorter following spinal analgesia (p = 000) or PCA (p < 000) than after epidural analgesia () Spinal analgesia (n = ). Received hyperbaric bupivacaine and diamorphine. () Epidural analgesia (n = ). Received bupivacaine and fentanyl. () PCA (n = ). Received intraoperative morphine and were then attached to a PCA device Patients (n = ) with colorectal disease undergoing laparoscopic large bowel resection. and exclusion criteria. Participants excluded after randomisation (n = ) -arm RCT. Adequate concealment Levy et al. () Blackwell Publishing Ltd Journal of Clinical Nursing

10 Review Facilitating early recovery of bowel motility after colorectal surgery 0 Table (Continued) Study Method Participants Intervention Outcomes Limitations/Notes Powered. MBP Time to first defecation (<00) was shorter in the probiotic group. No significant differences between groups in terms of LOS () Probiotics (n = ). Pre- and postoperative probiotic treatment. () Placebo control (n = ). Pre- and postoperative oral feeding with placebo Patients (n = ) with colorectal cancer undergoing an elective radical colorectomy. Clear description of inclusion and exclusion criteria. Participants excluded after randomisation (n = ) -arm RCT. Adequate concealment. Double-blinded. Placebo-controlled Liu et al. () trial. Outcome assessors blind to treatment status. Powered. MBP except prior to right hemicolectomy LOS (p = 000), time to first flatus (p = 000) and time to first defecation (p = 000) were shorter in the intervention group () Standard (n = 0). Standard fluid therapy, generally L water and mmol sodium. () Restricted (n = 0). Usually L water and mmol sodium Patients (n = ) undergoing elective hemicolectomy and sigmoidectomy for cancer. and exclusion criteria. Patients excluded after randomisation (n = ) -arm RCT. Adequate random allocation concealment Lobo et al. (0) Unclear whether the groups were treated identically. Withdrawals not mentioned Time to first flatus was shorter in the PTX group (p = 0000). No significant difference terms of LOS () Pentoxifylline (PTX) (n = ). Received PTX I.V. minutes. before surgery. () Control (n = ). Received the same volume saline drip Patients (n = ) undergoing elective colorectal cancer surgery. Clear description of inclusion and exclusion criteria -arm RCT. Adequate concealment. Double-blinded. Placebo-controlled Lu et al. (0) trial. Underpowered. MBP prior to left-sided surgery No significant differences terms of LOS, or time to first flatus or bowel movement () Standard (n = ). Received l 0 % saline and l % dextrose per day I.V., until POD. () Restricted (n = ). Received no intravenous fluids from POD Patients (n = 0) undergoing elective colorectal resection with primary anastomosis. Clear inclusion and exclusion criteria. Patients excluded after randomisation (n = ) -arm RCT. Adequate concealment. Blinded MacKay et al. (0) Attempt at blinding participants and healthcare providers. Underpowered No significant difference terms of LOS, or time to first flatus, bowel movement or defecation () Bracelet (placebo) (n = ). Acupressure bracelet worn on the wrist for minutes three times a day. () Gum chewing (n = ). Chewed gum for minutes three times a day. () Control (n = ). Standard of care Patients (n = ) undergoing elective partial colectomy due to colorectal cancer or benign conditions. and exclusion criteria -arm RCT. Adequate concealment. Placebo-controlled Matros et al. (0) Blackwell Publishing Ltd Journal of Clinical Nursing

11 Å Wallström and GH Frisman 0 Table (Continued) Study Method Participants Intervention Outcomes Limitations/Notes Very brief description of methods and results. Withdrawals not mentioned. Unclear whether the groups were treated identically LOS (p = 00) and time to first bowel movement (p = 00) were shorter in the intervention group for laparoscopic colectomy patients. No significant differences between the gum chewing group and the control arm for patients undergoing open colectomy () Gum chewing (n = ). Chewed one stick of gum for minutes () Control (n = ). No gum chewing Patients (n = ) undergoing elective colon resection. Unclear description of inclusion and exclusion criteria -arm RCT. Mentions but no description given McCormick et al. (0) trial. Mentions blinded healthcare providers in the water and carbohydrate groups, but no description given No significant difference in time to first flatus, although there was a trend towards earlier return in the carbohydrate group compared with the fasting group (p = 0) and water group (p = 0). Reduced LOS when comparing the carbohydrate (p = 00) group and the water group. A trend towards shorter LOS when comparing the carbohydrate (p = 00) group and the fasting group () Water (n = ). Received 00 mls of water the night before surgery and 0 mls hours before induction of anaesthesia. () Carbohydrate (n = ). Received Precarb. dissolved in 00 mls of water the night before surgery and Vitajoule dissolved in 0 mls of water hours before induction of anaesthesia. () Fasting (n = ). Fasting from midnight the night before surgery Patients (n = ) undergoing elective colorectal resections. and exclusion criteria. Participants excluded after randomisation (n = ) -arm RCT. Adequate concealment Noblett et al. (0a,b) trial. Underpowered LOS was shorter (p = 000) in the intervention group. No significant differences terms of time to first flatus or bowel movement () Intervention (n = ). Colloid boluses based on the assessment of an oesophageal Doppler probe. () Control (n = ). Intraoperative fluid in a conventional manner Patients (n = 0) undergoing elective colorectal resection. and exclusion criteria. Patients excluded after randomisation (n = ) -arm RCT. States but no description given. Blinded Noblett et al. (0a,b) Blackwell Publishing Ltd 0 Journal of Clinical Nursing

12 Review Facilitating early recovery of bowel motility after colorectal surgery 0 Table (Continued) Study Method Participants Intervention Outcomes Limitations/Notes Three patients in the gum chewing group did not receive the intervention. Powered. MBP No significant differences terms of LOS, or time to first flatus or first defecation Quah et al. (0) () Gum chewing (n = ). Chewed gum minutes three times daily POD. () Control (n = ). Standard postoperative care Patients (n = ) undergoing elective resection for left-sided colorectal cancer. and exclusion criteria -arm RCT. Adequate concealment trial. Divergent numbers for withdrawals. Underpowered. MBP Time to first flatus (p < 000) was shorter in the ketorolac group. There was no significant difference between the groups in terms of LOS () Ketorolac (n = ). Received ketorolac I.V. every hours for hours. () Control (n = ). Received saline placebo I.V. on the same schedule Patients (n = ) undergoing elective laparoscopic colon resection. and exclusion criteria. Participants excluded after randomisation (n = ) -arm RCT. Adequate concealment. Double-blinded. Placebo-controlled Schlachta et al. (0) Withdrawals not mentioned. Participants not treated identically. Brief description of methods LOS (p = 00) and time to first bowel movement (p = 00) were shorter in the intervention group. Time to first flatus was also shorter in the intervention group, but the difference was not significant (p = 00) () Gum chewing (n = ). Chewed gum three times a day, from POD until oral intake. () Control (n = ). No gum chewing Patients (n = ) undergoing sigmoid colon resection due to cancer or recurrent diverticular disease. Unclear description of inclusion and exclusion criteria -arm RCT. Adequate concealment Schuster et al. (0) Time to first bowel sound (p = 00), time to first flatus (p = 000) and time to first bowel movement (p = 00) were shorter in the intervention group. LOS (p = 000) was also shorter in the intervention group () Valdecoxib (n = ). Received valdecoxib orally hour < h before surgery. Doses were administered at hour intervals after the initial dose (up to hour). () Control (n = ). Received placebo at the same intervals Sim et al. (0) Patients (n = ) undergoing elective colorectal resection. and exclusion criteria -arm RCT. Adequate concealment. Double-blinded. Placebo-controlled Blackwell Publishing Ltd Journal of Clinical Nursing

13 Å Wallström and GH Frisman 0 Table (Continued) Study Method Participants Intervention Outcomes Limitations/Notes trial. A higher dose of lidocaine was given to half of the participants in the lidocaine group. Powered No significant differences terms of LOS, or time to first flatus or bowel movement () Lidocaine (n = ). Received an I.V. lidocaine infusion. () Epidural (n = ). Received a thoracic epidural with bupivacaine and hydromorphone Patients (n = ) undergoing elective colon resection. and exclusion criteria. Patients excluded after randomisation (n = ) -arm RCT. Adequate concealment Swenson et al. (0) trial. Received laxatives POD. Unclear whether the groups were treated identically. Unclear whether the patients were analysed in the groups they were originally allocated to. Powered LOS (p = 00) and time to first defecation (p = 00) were shorter in the fast-track groups than in the conventional care groups () Laparoscopy/fast track (n = ). Followed a fasttrack protocol. () Laparoscopy/standard (n = ). Followed a conventional care programme. () Open/fast track (n = ). Followed a fast-track protocol. () Open/standard (n = ). Followed a conventional care programme Patients (n = ) undergoing elective segmental colectomy for adenocarcinoma or adenoma without evidence of metastatic disease. and exclusion criteria. Patients excluded after randomisation (n = ) -arm RCT. Adequate concealment van Bree et al. () trial. Powered. MBP LOS (p = 00) and time to first defecation (p = 00) were shorter in the intervention group. No significant difference terms of time to first flatus () Doppler-guided fluid therapy (n = ). Received 0 ml boluses of colloid solution until the stroke volume failed to rise by 0% and/or the CVP rose by mmhg or more. () Control (n = ). Used CVP to guide I.V. fluid treatment. CVP was kept between mmhg Patients (n = ) undergoing elective or semi-elective colonic surgery. and exclusion criteria. Participants excluded after randomisation (n = ) -arm RCT. Adequate concealment. Blinded Wakeling et al. (0) trial. Powered. MBP prior to sigmoid and rectal surgery No significant differences terms of LOS, or time to first flatus or bowel movement (). Thoracic epidural catheter (TEA) (n = ). Received TEA with bupivacaine and morphine. () Intravenous lidocaine (IL) (n = ). Received IL via a PCA device Patients (n = ) undergoing elective laparoscopic colorectal resection. and exclusion criteria. Patients excluded after randomisation (n = ) -arm RCT. Adequate concealment Wongyingsinn et al. () Blackwell Publishing Ltd Journal of Clinical Nursing

14 Review Facilitating early recovery of bowel motility after colorectal surgery 0 Table (Continued) Study Method Participants Intervention Outcomes Limitations/Notes Withdrawals not mentioned Time to first flatus (p < 000) was shorter in the intervention group. No significant difference between groups in terms of LOS () Clonidine (n = ). Received PCEA with morphine and clonidine in ropivacaine. () Control (n = ). Received PCEA with morphine and ropivacaine Patients (n = ) undergoing elective colorectal surgery. Unclear description of inclusion and exclusion criteria -arm RCT. Mentions random allocation but no description given. Double-blinded. Placebo-controlled Wu et al. (0) Powered. MBP Time to first flatus (p = 00) and time to first bowel movement (p = 000) were shorter in the intervention group () Flurbiprofen axetil (n = ). Received flurbiprofen axetil I.V., minutes before and hours after skin incision. () Control (n = ) Received intralipid I.V. as placebo Patients (n = ) undergoing elective surgery for colorectal cancer. and exclusion criteria -arm RCT. Adequate random allocation concealment. Double-blinded. Placebo-controlled Xu et al. (0) trial. Powered. MBP prior to laparoscopic surgery Time to gastrointestinal recovery (p = 000) and first defecation (p = 000) was shorter in the intervention group. No significant difference time to first flatus () Bisacodyl (n = ). Received bisacodyl orally twice daily. The intervention period started one day before surgery and ended on POD. () Control (n = ). Received identical placebo capsules Patients (n = 0) undergoing open or laparoscopic colorectal resection. and exclusion criteria. Participants excluded after randomisation (n = ) -arm RCT. Adequate random allocation concealment. Double-blinded. Placebo-controlled Zingg et al. (0) MBP, mechanical bowel preparation; LOS, length of stay; PCA, patient-controlled analgesia; PCEA, patient-controlled epidural analgesia; POD, postoperative day; RCT, randomised controlled trial. Blackwell Publishing Ltd Journal of Clinical Nursing

15 Å Wallström and GH Frisman 0 Fluid therapy Restricted fluid therapy Postoperative fluid therapy was investigated in three studies (n = ) (Lobo et al. 0, MacKay et al. 0, Holte et al. 0), where a standard postoperative fluid therapy was compared with a restricted fluid therapy. In two studies (n = 0) (MacKay et al. 0, Holte et al. 0), no significant differences in gastrointestinal motility were found between the groups. However, by reducing both sodium and fluid, Lobo et al. (0) found significantly shorter times to first passage of flatus and first defecation, as well as shorter hospital stays. The three studies were assessed and shown to be comparative. Doppler-guided fluid therapy Two blinded studies (n = ) (Wakeling et al. 0, Noblett et al. 0a) were identified which compared standard fluid therapy with the use of an oesophageal Doppler (monitoring of cardiac output) as a guide in intraoperative fluid therapy. Random allocation concealment was mentioned but not described in one of the studies (n = ) (Noblett et al. 0a). No reduction in time to first passage of flatus was reported in the intervention groups, although length of hospital stay was significantly shorter in both studies. First defecation occurred significantly earlier in the intervention group, but was only measured in one study (Wakeling et al. 0). Laxative Bisacodyl One double-blinded, placebo-controlled study (n = ) (Zingg et al. 0) was identified which investigated preand postoperative use of bisacodyl. First defecation occurred significantly earlier in the intervention group, but there was no significant reduction in time to first passage of flatus or tolerance of solid food. Multimodal treatment Multimodal protocols Three studies (n = ) (Khoo et al. 0, Ionescu et al. 0, van Bree et al. ) have compared multimodal/ fast-track care to conventional care. The study protocols differed in a number of ways. Two of the studies (n = ) (Ionescu et al. 0, van Bree et al. ) included preoperative information and carbohydrate loading in their protocol. One of the study protocols (n = ) (Ionescu et al. 0) involved neither bowel cleaning/enema nor perioperative fluid restriction. Postoperative prokinetics were used in two of the studies (Khoo et al. 0, Ionescu et al. 0), while the third study used laxatives. All three studies were powered, but only one (Ionescu et al. 0) reached the estimated level of power. All studies showed a significantly reduced length of stay in hospital and a shorter time to restoration of bowel functions, measured in two of the studies (Khoo et al. 0, van Bree et al. ) as time to first defecation. Methods to decrease the use of opioids Flurbiprofen One double-blinded, placebo-controlled study (n = ) focused on the effect of intravenous flurbiprofen (NSAID) (Xu et al. 0). All participants received analgesia (morphine, ropivacaine and sodium chloride) through a thoracic epidural catheter. Flurbiprofen was administrated pre- and postoperatively and led to a significantly reduced time to first passage of flatus. Ketorolac The effect of intravenous ketorolac (NSAID) was investigated in three double-blinded studies (n = ) (Chen et al. 0, 0, Schlachta et al. 0). Two of the studies (n = ) (Chen et al. 0, 0) compared the effect of ketorolac and morphine administered through a PCA device with the effect of morphine administered in the same way. It was unclear whether the participants in the study by Chen et al. (0) (n = ) were treated identically, other than for named interventions. Both studies showed a significantly reduced time to bowel movements in the ketorolac group, but time to first flatus was only significantly shorter in one study (Chen et al. 0). Length of hospital stay was measured in one of the studies (Chen et al. 0), but the difference was not significant. The third study (Schlachta et al. 0) was placebo-controlled except for the blinding and evaluated the effect of ketorolac administered intravenously after laparoscopic surgery. All participants received intravenous morphine administrated through a PCA device. The quality of this study was assessed as low for reasons listed in Table. The study was powered, but was a long way from the estimated level of power. The overall incidence of anastomotic leaks in this study was %, compared with % among the participants who received ketorolac. Passage of first flatus occurred significantly earlier in the intervention group, but the intervention did not lead to a reduction in length of hospital stay. Blackwell Publishing Ltd Journal of Clinical Nursing

16 Review Facilitating early recovery of bowel motility after colorectal surgery 0 Valdecoxib Participants in a blinded and placebo-controlled study (n = ) (Sim et al. 0) received valdecoxib (NSAID) orally. All participants received intravenous morphine administered through a PCA device. One dose was given prior to surgery, and several doses were administered postoperatively. Valdecoxib generated significantly earlier passage of flatus, defecation and bowel movement compared with placebo treatment. The length of hospital stay was also significantly reduced. Intravenous lidocaine The use of intravenous lidocaine was examined in three studies (n = ) (Herroeder et al. 0, Swenson et al. 0, Wongyingsinn et al. ). Two studies (n = 0) (Swenson et al. 0, Wongyingsinn et al. ) evaluated the effect of intravenous lidocaine versus thoracic epidural with bupivacaine. The effect of lidocaine on time to first passage of flatus, first bowel movements and length of hospital stay was not significant in either study. The third study was double-blinded and placebo-controlled, and focused on the effect of intravenous lidocaine compared with placebo. The intervention led to significantly earlier bowel movement, earlier passage of flatus and reduced length of hospital stay. The three studies were assessed and shown to be comparative. Ropivacaine The use of local anaesthetics such as ropivacaine was examined in one study (n = ) (Beaussier et al. 0). Ropivacaine was administered as a continuous wound infusion as soon as the surgical wound was closed. The study was double-blinded and placebo-controlled. Time to first passage of flatus did not differ significantly between the groups, but the intervention resulted in significantly reduced time to first defecation and reduced length of hospital stay. Intrathecal morphine The effect of intrathecal morphine on recovery in older patients was analysed in a double-blinded, placebocontrolled study (n = ) (Beaussier et al. 0). No significant reductions were seen in time to first passage of flatus or length of hospital stay. Epidural clonidine A double-blinded, placebo-controlled study (n = ) (Wu et al. 0) was identified which evaluated the effect of epidural Clonidine (adrenergic agonist). The study lacked descriptions of how blinding of healthcare providers was established, inclusion and exclusion criteria, and descriptions of concealment. Time to first passage of flatus was significantly shorter in the intervention group, but the intervention did not lead to a reduction in length of hospital stay. Spinal analgesia One study (n = ) (Levy et al. ) compared spinal, epidural and intravenous (patient-controlled) analgesia. Spinal analgesia resulted in significantly earlier restoration of bowel function compared with epidural and patient-controlled analgesia. Both spinal and patient-controlled analgesia reduced the length of hospital stay significantly compared with epidural analgesia. Other pharmacological treatment Choline citrate Choline citrate is a supplement in the vitamin B complex group. One study (n = 0) (Herzog et al. ) investigated the effect of choline citrate on patients with POI hours after surgery. The study was placebo-controlled, was double-blinded and stated that randomisation was performed postoperatively, although no description was given. No significant results were found regarding time to first passage of flatus, time to first defecation or length of hospital stay. Intravenous pentoxifylline One study (n = ) (Lu et al. 0) analysed preoperative intravenous pentoxifylline (cytokine inhibitors) treatment as an intervention for improving the recovery of bowel functions. The study was double-blinded and placebo-controlled. Whether the groups were treated identically after the operation is unclear. The intervention resulted in significantly earlier passage of flatus, but no reduction in length of hospital stay. Non-pharmacological interventions Muscle relaxation and guided imagery Psychological interventions such as muscle relaxation therapy and guided imagery were compared to standard care in a blinded, age-stratified study (n = 0) (Haase et al. 0). There was no reduction in time to first passage of flatus, first bowel movement or length of hospital stay in the intervention group. Discussion The review revealed that recovery of gastrointestinal motility was accelerated with multimodal treatment, probiotics, Blackwell Publishing Ltd Journal of Clinical Nursing

17 Å Wallström and GH Frisman 0 pentoxifylline, flurbiprofen, valdecoxib, ketorolac, clonidine, ropivacaine and spinal analgesia. Nutrition through early feeding did not, in itself, lead to faster gastrointestinal recovery, but when it was included in a simplified pathway, the difference was found to be significant compared with standard care. Intravenous lidocaine was found to accelerate the return of gastrointestinal motility, but the difference was not significant compared with epidural analgesia. The effect of gum chewing, preoperative carbohydrate loading, bisacodyl and Doppler-guided fluid management was uncertain. Hence, the use of non-pharmacological interventions, intrathecal morphine, restricted fluid therapy and choline citrate did not lead to a significant acceleration in bowel motility. Three multimodal approaches were found to accelerate the return of gastrointestinal motility (Khoo et al. 0, Ionescu et al. 0, van Bree et al. ). The content of the optimal multimodal protocol is constantly evolving as research results support the introduction of new treatment strategies. Unfortunately, compliance with evidence-based treatment strategies is low, as seen in the survey conducted by Kehlet et al. 0, which may influence patients negatively. However, there is a gap in the literature regarding the current most optimal composition of treatment protocols, and larger specific multicentre studies are needed to obtain sustainable evidence. Also, with an ageing population in mind, treatment protocols should be properly adjusted for older patients with comorbidity. This review revealed both beneficial and ineffectual interventions, suggesting that future studies that focus on the composition of multimodal protocols will be of great importance. The latest and most comprehensive review, written by the Enhanced Recovery After Surgery (ERAS) group, was published in 0 and presented a model for optimal perioperative care in colorectal surgery (Lassen et al. 0). Multimodal treatment is often studied from a medical point of view and lacks a patient perspective, which is remarkable as multimodal regimes are demanding for patients in a fragile situation. Patient empowerment plays a key role during postoperative recovery (Fearon et al. 0). Norlyk and Harder (0) describe how the patient struggles against the body to overcome the dilemma, whether by listening to the body s signals or by following the regimen, which might explain why protocol compliance is low in the immediate postoperative phase (Maessen et al. 0). To be able to mobilise energy to carry out the regimen, patients need support from professionals, involving trust and a sense of security (Norlyk & Harder 0). A common concern voiced by critics of fast-track care is whether it increases rates of complication and readmission, which would contribute to increased hospitalisation costs and longer hospital stays. Two studies evaluated the readmission rate after fast-track care compared with standard care, but did not find any significant differences between the treatments (Gouvas et al. 0, Teeuwen et al. ). However, successful early discharge within a fast-track programme demands well-structured postdischarge followup, including well-defined ways for patients to contact their healthcare providers for advice (Taylor & Burch ). Interventions that resulted in earlier restoration of gastrointestinal bowel motility were not always associated with a reduced stay in hospital (Lu et al. 0, Wu et al. 0, Chen et al. 0, Schlachta et al. 0, Liu et al. ). Possible reasons for this may be inadequate pain management, wound infections or a negative electrolyte balance. A study by Aarts et al. () identified five factors associated with a reduced stay in hospital. The study was based on ERAS components and concluded that preoperative counselling, a laparoscopic approach, intraoperative fluid restriction, early intake of clear fluids and early removal of the urinary catheter resulted in a hospital stay of five days. Reduced gut motility is a well-known side effect of opioids (Bueno & Fioramonti ), which explains the value of restricted opioid use during the postoperative phase. This review indicates that non-steroidal anti-inflammatory drugs (NSAID) such as flurbiprofen and ketorolac might be helpful in restricting opioid use (Chen et al. 0, 0, Schlachta et al. 0, Sim et al. 0). Although the use of valdecoxib (Sim et al. 0) led to earlier restoration of gastrointestinal bowel motility, cardiovascular toxicity meant that the drug was withdrawn from the market. Epidural analgesia is considered to be effective in pain management in colorectal surgery and has a positive impact on surgical stress response (Lassen et al. 0). The comparison by Levy et al. () between PCA, spinal analgesia and epidural analgesia showed spinal analgesia to be preferable in laparoscopic colonic surgery. More research is needed to evaluate the effects of spinal analgesia in open colorectal resections. Several studies have concluded that postoperative gum chewing is safe, inexpensive and easy to implement. However, this review questioned the effect of gum chewing on the early restoration of gastrointestinal functions, as many of the studies were of poor quality. On the other hand, a meta-analysis of the same studies by Parnaby et al. (0) concluded that postoperative gum Blackwell Publishing Ltd Journal of Clinical Nursing

18 Review Facilitating early recovery of bowel motility after colorectal surgery 0 chewing accelerates the restoration of gastrointestinal functions. Nevertheless, the authors argued that the findings were of limited value as the studies were significantly heterogeneous. In this review, passage of flatus, defecation and bowel movement were used as outcome measures to evaluate gastrointestinal bowel motility. Passage of flatus and defecation have been defined as indicators of restored bowel motility after surgery (Delaney et al. 0). Bowel movement, on the other hand, may be mistaken for movement in the small bowel. All three outcome measures were important, although it could be argued that passage of flatus was the most reliable. The value of bowel movement as an outcome measure should be questioned, if used solely. Where they occur soon after colorectal surgery, they may be due to small bowel activity and therefore do not necessarily indicate recovery of gastrointestinal motility (Huge et al. 00). However, used in a context of other factors, bowel movement may be helpful as an outcome measure when evaluating recovery of bowel motility. A consensus on accurate outcome measures would be useful in improving the validity of studies that measure gastrointestinal recovery. A number of studies made use of preoperative mechanical bowel preparation. According to Jung et al. (0), mechanical bowel preparation causes discomfort in patients and prolongs POI. This implies that, in the studies that were reviewed, mechanical bowel preparation may have had an impact on the outcome measures for gastrointestinal recovery. The pre- and postoperative use of bisacodyl led to earlier postoperative defecation, but it is unclear whether the gastrointestinal function was accelerated, as there was no reduction either in the time taken to restore passage of flatus or the time taken to restore tolerance of solid food. Psychological interventions such as muscle relaxation therapy and guided imagery did not restore gastrointestinal functions more quickly, although % of participants in the study thought they had benefited from listening to the tapes and a majority stated that they would recommend it to others (Haase et al. 0). This indicates that a psychological effect played an important role in their postoperative recovery, at least subjectively. The results of this review indicate that restricted fluid therapy does not result in faster gastrointestinal recovery, but that restricted fluid therapy with less sodium does. A meta-analysis to compare restricted fluid therapy, standard fluid therapy and guided fluid therapy (oesophageal Doppler) did not show any significant differences in recovery of bowel functions or in the length of stay in hospital, but concluded that the risk of cardio and pulmonary complication makes restricted fluid therapy more favourable than standard fluid therapy (Rahbari et al. 0). Five of the nine studies subjected to the meta-analysis were included in this review. A recent study evaluating the effects of restricted perioperative fluid therapy confirmed that the result for length of stay in hospital was not significant (Abraham-Nordling et al. ). The studies reviewed in the analysis consisted almost solely of elective surgeries, although a considerable amount of colorectal surgery is acute. Future research should evaluate whether the interventions mentioned above have the same effect in acute care surgery and, if they do not, how they could be modified to aid a faster recovery. Some methodological issues require consideration and may limit the conclusions drawn from this review. The literature search was narrowed to the last ten years of research, but the RCT limit had the biggest impact on the search response. The RCT limit was used as RCTs produce the highest levels of evidence (Cochrane Consumer Network 0). The review only involved studies written in English and may therefore have excluded important studies (publication bias) written in other languages. The studies that formed part of the review were small, with a mean sample size of participants, ranging from participants. Taken alongside the fact that seven studies were underpowered, the differences between groups have to be bigger to be considered statistically significant. A quality assessment of all the studies focused on selection bias at trial entry, around the time of treatment, during assessment of outcomes or at the analysis stage. Individual components were used to show the importance of quality, as suggested by Juni et al. (0), rather than a quality scale. This may have introduced a degree of subjectivity into the author s interpretation, and an attempt was made to reduce this potential bias by asking a second reviewer to conduct an independent quality assessment of the studies. The blinding was difficult to assess in some of the studies, as there was often no description of the procedure, even though the authors mentioned that blinding had been used. The assessment of whether the groups had been treated identically, other than for named interventions, was also problematic, as postoperative care descriptions were not specific in a number of studies. A well-described and wellexecuted blinding procedure, along with stringent identical treatment of groups, is essential if performance bias is to be Blackwell Publishing Ltd Journal of Clinical Nursing

19 Å Wallström and GH Frisman 0 avoided and internal validity is to be preserved (Juni et al. 0). Most of the studies stated that the results were analysed on an intention-to-treat basis, but only studies applied a strict definition of intention to treat (Gunnarsson 0). According to Roe (0), there is a risk of overestimating the effects of treatment if a study does not analyse all the subjects. conclusion Multimodal treatment, where the use of morphine is restricted, seems to be the best way of accelerating the recovery of gastrointestinal bowel motility. More studies are required to examine the content of multimodal protocols and how patients experience them. Future research should also focus on how multimodal protocols can be optimised for both elective and acute colorectal surgery. References Abraham-Nordling M, Hjern F, Pollack J, Prytz M, Borg T & Kressner U () Randomized clinical trial of fluid restriction in colorectal surgery. The British Journal of Surgery,. Allvin R, Ehnfors M, Rawal N & Idvall E (0) Experiences of the postoperative recovery process: an interview study. The Open Nursing Journal,. Artinyan A, Nunoo-Mensah JW, Balasubramaniam S, Gauderman J, Essani R, Gonzalez-Ruiz C, Kaiser AM & Beart RW Jr (0) Prolonged postoperative ileus-definition, risk factors, and predictors after surgery. World Journal of Surgery, 0. Asao T, Kuwano H, Nakamura J, Morinaga N, Hirayama I & Ide M (0) Gum chewing enhances early recovery from postoperative ileus after laparoscopic colectomy. Journal of the American College of Surgeons,. Beaussier M, Weickmans H, Parc Y, Delpierre E, Camus Y, Funck-Brentano C, Schiffer E, Delva E & Lienhart A (0) Postoperative analgesia and recovery course after major colorectal surgery in elderly patients: a randomized comparison between intrathecal morphine and intravenous PCA morphine. Regional Anesthesia and Pain Medicine,. Relevance to clinical practice Early restoration of bowel functions leads to faster overall postoperative recovery, which may ease patient discomfort and decrease hospitalisation costs. Acknowledgements The authors would like to express their thanks to the staff at the Faculty of Health Science Library at Linköping University for their help and encouragement. Contributions The County Council of Östergötland. Conflict of interest Beaussier M, El Ayoubi H, Schiffer E, Rollin M, Parc Y, Mazoit JX, Azizi L, Gervaz P, Rohr S, Biermann C, Lienhart A & Eledjam JJ (0) Continuous preperitoneal infusion of ropivacaine provides effective analgesia and accelerates recovery after colorectal surgery: a randomized, double-blind, placebo-controlled study. Anesthesiology 0,. Börjeson S, Arwestrom C, Baker A & Bertero C (0) Nurses experiences in the relief of postoperative nausea and vomiting. Journal of Clinical Nursing,. van Bree SH, Vlug MS, Bemelman WA, Hollmann MW, Ubbink DT, Zwinderman AH, de Jonge WJ, Snoek SA, Bolhuis K, van der Zanden E, The FO, Bennink RJ & Boeckxstaens GE () Faster recovery of gastrointestinal transit after laparoscopy and fast-track care in patients undergoing colonic surgery. Gastroenterology, 0.e. Bueno L & Fioramonti J () Action of opiates on gastrointestinal function. Bailliere s Clinical Gastroenterology,. Chen JY, Wu GJ, Mok MS, Chou YH, Sun WZ, Chen PL, Chan WS, Yien HW & Wen YR (0) Effect of adding ketorolac to intravenous morphine patient-controlled analgesia on bowel There are no conflicts of interest to declare. function in colorectal surgery patients a prospective, randomized, doubleblind study. Acta Anaesthesiologica Scandinavica,. Chen JY, Ko TL, Wen YR, Wu SC, Chou YH, Yien HW & Kuo CD (0) Opioid-sparing effects of ketorolac and its correlation with the recovery of postoperative bowel function in colorectal surgery patients: a prospective randomized double-blinded study. The Clinical Journal of Pain,. Cochrane Consumer Network (0) Levels of evidence. The Cochrane Collaboration. Available at: consumers.cochrane.org/levels-evidence (accessed XX Xxxxx XX). Condon RE, Cowles VE, Ferraz AA, Carilli S, Carlson ME, Ludwig K, Tekin E, Ulualp K, Ezberci F & Shoji Y () Human colonic smooth muscle electrical activity during and after recovery from postoperative ileus. The American Journal of Physiology, G G. Delaney CP, Weese JL, Hyman NH, Bauer J, Techner L, Gabriel K, Du W, Schmidt WK & Wallin BA & Alvimopan Postoperative Ileus Study Group (0) Phase III trial of alvimopan, a novel, peripherally acting, mu opioid antagonist, for postoperative ileus after major abdominal surgery. Diseases Blackwell Publishing Ltd Journal of Clinical Nursing

20 Review Facilitating early recovery of bowel motility after colorectal surgery 0 of the Colon and Rectum, ; discussion ; author reply. Delaney C, Kehlet H, Senagore A, Bauer A, Beart R, Billingham R, Coleman RL, Dozois EJ, Leslie JB, Marks J, Megibow AJ, Michelassi F & Steinbrook RA (0) Postoperative ileus: profiles, risk factors, and definitions a framework for optimizing surgical outcomes in patients undergoing major abdominal and colorectal surgery. Clinical Consensus Update in General Surgery,. Fearon KC, Ljungqvist O, Von Meyenfeldt M, Revhaug A, Dejong CH, Lassen K, Nygren J, Hausel J, Soop M, Andersen J & Kehlet H (0) Enhanced recovery after surgery: a consensus review of clinical care for patients undergoing colonic resection. Clinical Nutrition (Edinburgh, Scotland),. Feo CV, Romanini B, Sortini D, Ragazzi R, Zamboni P, Pansini GC & Liboni A (0) Early oral feeding after colorectal resection: a randomized controlled study. ANZ Journal of Surgery,. da Fonseca LM, Profeta da Luz MM, Lacerda-Filho A, Correia MI & Gomes da Silva R () A simplified rehabilitation program for patients undergoing elective colonic surgery -randomized controlled clinical trial. International Journal of Colorectal Disease, 0. Gatt M, Anderson AD, Reddy BS, Hayward-Sampson P, Tring IC & MacFie J (0) Randomized clinical trial of multimodal optimization of surgical care in patients undergoing major colonic resection. The British Journal of Surgery,. Gervaz P, Bucher P, Scheiwiller A, Mugnier- Konrad B & Morel P (0) The duration of postoperative ileus after elective colectomy is correlated to surgical specialization. International Journal of Colorectal Disease,. Goldstein J, Matuszewski K, Delaney C, Senagore A, Chiao E, Shah M, Meyer K & Bramley T (0) Inpatient economic burden of postoperative ileus associated with abdominal surgery in the United States. Pharmacy and Therapeautics, 0. Gouvas N, Tan E, Windsor A, Xynos E & Tekkis PP (0) Fast-track vs standard care in colorectal surgery: a meta-analysis update. International Journal of Colorectal Disease,. Grant AM, Cody DJ & Glazener CMA & et al. (eds) (0) Assessment of Quality of Trial Methodology for the Cochrane Incontinence Group. The Cochrane Collaboration (Cochrane Review Groups) 00, Issue 0. Available at: wiley.com/o/cochrane/clabout/articles/ INCONT/frame.html (accessed XX ; Xxxxx XX). Gunnarsson R (0) Intention to treat/per protocol. Dept of Prim Health Care Göteborg University - Research Methodology Web Site 0. Available at: (accessed XX Xxxxx XX). Haase O, Schwenk W, Hermann C & Muller JM (0) Guided imagery and relaxation in conventional colorectal resections: a randomized, controlled, partially blinded trial. Diseases of the Colon and Rectum,. Habib AS & Gan TJ (0) Evidence-based management of postoperative nausea and vomiting: a review. Canadian Journal of Anaesthesia,. Han-Geurts IJ, Hop WC, Kok NF, Lim A, Brouwer KJ & Jeekel J (0) Randomized clinical trial of the impact of early enteral feeding on postoperative ileus and recovery. The British Journal of Surgery,. Herroeder S, Pecher S, Schonherr ME, Kaulitz G, Hahnenkamp K, Friess H, Bottiger BW, Bauer H, Dijkgraaf MG, Durieux ME & Hollmann MW (0) Systemic lidocaine shortens length of hospital stay after colorectal surgery: a double-blinded, randomized, placebo-controlled trial. Annals of Surgery, 0. Herzog T, Lemmens HP, Arlt G, Raakow R, Weimann A, Pascher A, Knoefel WT, Hesse U, Scheithe K, Groll S & Uhl W () Treatment of postoperative ileus with choline citrate results of a prospective, randomised, placebocontrolled, double-blind multicentre trial. International Journal of Colorectal Disease,. Hirayama I, Suzuki M, Ide M, Asao T & Kuwano H (0) Gum-chewing stimulates bowel motility after surgery for colorectal cancer. Hepato-Gastroenterology,. Holte K & Kehlet H (00) Postoperative ileus: a preventable event. The British Journal of Surgery,. Holte K & Kehlet H (0) Postoperative ileus: progress towards effective management. Drugs, 0. Holte K, Foss NB, Andersen J, Valentiner L, Lund C, Bie P & Kehlet H (0) Liberal or restrictive fluid administration in fast-track colonic surgery: a randomized, double-blind study. British Journal of Anaesthesia, 0. Huge A, Kreis ME, Zittel TT, Becker HD, Starlinger MJ & Jehle EC (00) Postoperative colonic motility and tone in patients after colorectal surgery. Diseases of the Colon and Rectum,. Ionescu D, Iancu C, Ion D, Al-Hajjar N, Margarit S, Mocan L, Mocan T, Deac D, Bodea R & Vasian H (0) Implementing fast-track protocol for colorectal surgery: a prospective randomized clinical trial. World Journal of Surgery,. Iyer S, Saunders WB & Stemkowski S (0) Economic burden of postoperative ileus associated with colectomy in the United States. Journal of Managed Care Pharmacy,. Jonsson CA, Stenberg A & Frisman GH () The lived experience of the early postoperative period after colorectal cancer surgery. European Journal of Cancer Care,. Jung B, Lannerstad O, Pahlman L, Arodell M, Unosson M & Nilsson E (0) Preoperative mechanical preparation of the colon: the patient s experience. BMC Surgery,. Juni P, Altman DG & Egger M (0) Systematic reviews in health care: assessing the quality of controlled clinical trials. BMJ (Clinical Research Ed.),. Kehlet H (00) Postoperative ileus. Gut (Suppl ), iv iv; discussion iv. Kehlet H, Buchler MW, Beart RW Jr, Billingham RP & Williamson R (0) Care after colonic operation is it evidence-based? Results from a multinational survey in Europe and the United States. Journal of the American College of Surgeons,. Blackwell Publishing Ltd Journal of Clinical Nursing

21 Å Wallström and GH Frisman 0 Kerger H, Turan A, Kredel M, Stuckert U, Alsip N, Gan TJ & Apfel CC (0) Patients willingness to pay for antiemetic treatment. Acta Anaesthesiologica Scandinavica,. Khoo CK, Vickery CJ, Forsyth N, Vinall NS & Eyre-Brook IA (0) A prospective randomized controlled trial of multimodal perioperative management protocol in patients undergoing elective colorectal resection for cancer. Annals of Surgery,. Lassen K, Soop M, Nygren J, Cox PB, Hendry PO, Spies C, von Meyenfeldt MF, Fearon KC, Revhaug A, Norderval S, Ljungqvist O, Lobo DN & Dejong CH & Enhanced Recovery After Surgery (ERAS) Group (0) Consensus review of optimal perioperative care in colorectal surgery: Enhanced Recovery After Surgery (ERAS) Group recommendations. Archives of Surgery (Chicago, IL.: 0),. Levy BF, Scott MJ, Fawcett W, Fry C & Rockall TA () Randomized clinical trial of epidural, spinal or patientcontrolled analgesia for patients undergoing laparoscopic colorectal surgery. The British Journal of Surgery, 0 0. Liu Z, Qin H, Yang Z, Xia Y, Liu W, Yang J, Jiang Y, Zhang H, Yang Z, Wang Y & Zheng Q () Randomised clinical trial: the effects of perioperative probiotic treatment on barrier function and post-operative infectious complications in colorectal cancer surgery a double-blind study. Alimentary Pharmacology & Therapeutics,. Livingston EH & Passaro EP Jr (0) Postoperative ileus. Digestive Diseases and Sciences,. Lloyd GM, Kirby R, Hemingway DM, Keane FB, Miller AS & Neary P (0) The RAPID protocol enhances patient recovery after both laparoscopic and open colorectal resections. Surgical Endoscopy,. Lobo DN, Bostock KA, Neal KR, Perkins AC, Rowlands BJ & Allison SP (0) Effect of salt and water balance on recovery of gastrointestinal function after elective colonic resection: a randomised controlled trial. Lancet,. Lu CH, Chao PC, Borel CO, Yang CP, Yeh CC, Wong CS & Wu CT (0) Preincisional intravenous pentoxifylline attenuating perioperative cytokine response, reducing morphine consumption, and improving recovery of bowel function in patients undergoing colorectal cancer surgery. Anesthesia and Analgesia, ; table of contents. MacKay G, Fearon K, McConnachie A, Serpell MG, Molloy RG & O Dwyer PJ (0) Randomized clinical trial of the effect of postoperative intravenous fluid restriction on recovery after elective colorectal surgery. The British Journal of Surgery,. Maessen J, Dejong CH, Hausel J, Nygren J, Lassen K, Andersen J, Kessels AG, Revhaug A, Kehlet H, Ljungqvist O, Fearon KC & von Meyenfeldt MF (0) A protocol is not enough to implement an enhanced recovery programme for colorectal resection. The British Journal of Surgery,. Matros E, Rocha F, Zinner M, Wang J, Ashley S, Breen E, Soybel D, Shoji B, Burgess A, Bleday R, Kuntz R & Whang E (0) Does gum chewing ameliorate postoperative ileus? Results of a prospective, randomized, placebocontrolled trial. Journal of the American College of Surgeons,. Mattei P & Rombeau JL (0) Review of the pathophysiology and management of postoperative ileus. World Journal of Surgery,. McCormick JT, Garvin R, Caushaj P, Simmang C, Gregorcyk S, Huber P, Odom C, Downs M, Read T & Papaconstantinou H (0) The effects of gum-chewing on bowel function and hospital stay after laparoscopic vs open colectomy: a multi-institutional prospective randomized trial. Journal of the American College of Surgeons,. Morson BC, Dawson IMP & Day DW (0). Morson & Dawson s Gastrointestinal Pathology. Blackwell, Oxford. Nisanevich V, Felsenstein I, Almogy G, Weissman C, Einav S & Matot I (0) Effect of intraoperative fluid management on outcome after intraabdominal surgery. Anesthesiology 0,. Noblett SE, Snowden CP, Shenton BK & Horgan AF (0a) Randomized clinical trial assessing the effect of Doppler-optimized fluid management on outcome after elective colorectal resection. The British Journal of Surgery, 0 0. Noblett SE, Watson DS, Huong H, Davison B, Hainsworth PJ & Horgan AF (0b) Pre-operative oral carbohydrate loading in colorectal surgery: a randomized controlled trial. Colorectal Disease,. Norlyk A & Harder I (0) After colonic surgery: the lived experience of participating in a fast-track programme. International Journal of Qualitative Studies on Health and Well-being, 0 0. Parnaby CN, MacDonald AJ & Jenkins JT (0) Sham feed or sham? A metaanalysis of randomized clinical trials assessing the effect of gum chewing on gut function after elective colorectal surgery. International Journal of Colorectal Disease,. Quah HM, Samad A, Neathey AJ, Hay DJ & Maw A (0) Does gum chewing reduce postoperative ileus following open colectomy for left-sided colon and rectal cancer? A prospective randomized controlled trial. Colorectal Disease, 0. Rahbari NN, Zimmermann JB, Schmidt T, Koch M, Weigand MA & Weitz J (0) Meta-analysis of standard, restrictive and supplemental fluid administration in colorectal surgery. The British Journal of Surgery,. Roe B (0). Key stages and considerations when undertaking a systematic review: Bladder Training for the management of urinary incontinence. In Reviewing Research Evidence for Nursing Practice. (Roe B & Webb C eds). Blackwell Publishing Ltd, Oxford, pp.. Schlachta CM, Burpee SE, Fernandez C, Chan B, Mamazza J & Poulin EC (0) Optimizing recovery after laparoscopic colon surgery (ORAL-CS): effect of intravenous ketorolac on length of hospital stay. Surgical Endoscopy,. Schuster R, Grewal N, Greaney GC & Waxman K (0) Gum chewing reduces ileus after elective open sigmoid colectomy. Archives of Surgery (Chicago, Ill.: 0),. Blackwell Publishing Ltd Journal of Clinical Nursing

22 Review Facilitating early recovery of bowel motility after colorectal surgery 0 Serclova Z, Dytrych P, Marvan J, Nova K, Hankeova Z, Ryska O, Slegrova Z, Buresova L, Travnikova L & Antos F (0) Fast-track in open intestinal surgery: prospective randomized study (Clinical Trials Gov Identifier no. NCT00). Clinical Nutrition (Edinburgh, Scotland),. Sim R, Cheong DM, Wong KS, Lee BM & Liew QY (0) Prospective randomized, double-blind, placebo-controlled study of pre- and postoperative administration of a COX--specific inhibitor as opioid-sparing analgesia in major colorectal surgery. Colorectal Disease, 0. Suehiro T, Matsumata T, Shikada Y & Sugimachi K (0) The effect of the herbal medicines dai-kenchu-to and keishi-bukuryo-gan on bowel movement after colorectal surgery. Hepato- Gastroenterology, 00. Swenson BR, Gottschalk A, Wells LT, Rowlingson JC, Thompson PW, Barclay M, Sawyer RG, Friel CM, Foley E & Durieux ME (0) Intravenous lidocaine is as effective as epidural bupivacaine in reducing ileus duration, hospital stay, and pain after open colon resection: a randomized clinical trial. Regional Anesthesia and Pain Medicine,. Taylor C & Burch J () Feedback on an enhanced recovery programme for colorectal surgery. British Journal of Nursing (Mark Allen Publishing),. Teeuwen PH, Bleichrodt RP, de Jong PJ, van Goor H & Bremers AJ () Enhanced recovery after surgery versus conventional perioperative care in rectal surgery. Diseases of the Colon and Rectum,. Wakeling HG, McFall MR, Jenkins CS, Woods WG, Miles WF, Barclay GR & Fleming SC (0) Intraoperative oesophageal Doppler guided fluid management shortens postoperative hospital stay after major bowel surgery. British Journal of Anaesthesia,. Waldhausen JH, Shaffrey ME, Skenderis BS II, Jones RS & Schirmer BD (0) Gastrointestinal myoelectric and clinical patterns of recovery after laparotomy. Annals of Surgery, ; discussion. Wilson JP () Postoperative motility of the large intestine in man. Gut,. Wolff BG, Viscusi ER, Delaney CP, Du W & Techner L (0) Patterns of gastrointestinal recovery after bowel resection and total abdominal hysterectomy: pooled results from the placebo arms of alvimopan phase III North American clinical trials. Journal of the American College of Surgeons,. Wongyingsinn M, Baldini G, Charlebois P, Liberman S, Stein B & Carli F () Intravenous lidocaine versus thoracic epidural analgesia: a randomized controlled trial in patients undergoing laparoscopic colorectal surgery using an enhanced recovery program. Regional Anesthesia and Pain Medicine,. Worster B & Holmes S (0) A phenomenological study of the postoperative experiences of patients undergoing surgery for colorectal cancer. European Journal of Oncology Nursing,. Wu CT, Jao SW, Borel CO, Yeh CC, Li CY, Lu CH & Wong CS (0) The effect of epidural clonidine on perioperative cytokine response, postoperative pain, and bowel function in patients undergoing colorectal surgery. Anesthesia and Analgesia,, table of contents. Xu Y, Tan Z, Chen J, Lou F & Chen W (0) Intravenous flurbiprofen axetil accelerates restoration of bowel function after colorectal surgery. Canadian Journal of Anaesthesia = Journal Canadien d Anesthesie,. Zingg U, Miskovic D, Pasternak I, Meyer P, Hamel CT & Metzger U (0) Effect of bisacodyl on postoperative bowel motility in elective colorectal surgery: a prospective, randomized trial. International Journal of Colorectal Disease,. Zingg U, Miskovic D, Hamel CT, Erni L, Oertli D & Metzger U (0) Influence of thoracic epidural analgesia on postoperative pain relief and ileus after laparoscopic colorectal resection : benefit with epidural analgesia. Surgical Endoscopy,. The Journal of Clinical Nursing (JCN) is an international, peer reviewed journal that aims to promote a high standard of clinically related scholarship which supports the practice and discipline of nursing. For further information and full author guidelines, please visit JCN on the Wiley Online Library website: wileyonlinelibrary.com/journal/jocn Reasons to submit your paper to JCN: High-impact forum: one of the world s most cited nursing journals, with an impact factor of ranked / (Nursing (Social Science)) and / Nursing (Science) in the Journal Citation Reports â (Thomson Reuters, ). One of the most read nursing journals in the world: over million full text accesses in and accessible in over 000 libraries worldwide (including over 00 in developing countries with free or low cost access). Early View: fully citable online publication ahead of inclusion in an issue. Fast and easy online submission: online submission at Positive publishing experience: rapid double-blind peer review with constructive feedback. Online Open: the option to make your article freely and openly accessible to non-subscribers upon publication in Wiley Online Library, as well as the option to deposit the article in your preferred archive. Blackwell Publishing Ltd Journal of Clinical Nursing

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25 T H C H C y H y y y T y H C C C y y O n c e y o u h a v e A c r o b a t R e a d e r o p e n o n y o u r c o m p u t e r, c l i c k o n t h e C o m m e n t t a b a t t h e r i g h t o f t h e t o o l b a r : h i s w i l l o p e n u p a p a n e l d o w n t h e r i g h t s i d e o f t h e d o c u m e n t. h e m a j o r i t o f t o o l s o u w i l l u s e f o r a n n o t a t i n g o u r p r o o f w i l l b e i n t h e A n n o t a t i o n s s e c t i o n, p i c t u r e d o p p o s i t e. W e v e p i c k e d o u t s o m e o f t h e s e t o o l s b e l o w : S t r i k e s a l i n e t h r o u g h t e x t a n d o p e n s u p a t e x t b o x w h e r e r e p l a c e m e n t t e x t c a n b e e n t e r e d. S t r i k e s a r e d l i n e t h r o u g h t e x t t h a t i s t o b e d e l e t e d. i g h l i g h t a w o r d o r s e n t e n c e. l i c k o n t h e R e p l a c e ( I n s ) i c o n i n t h e A n n o t a t i o n s s e c t i o n. i g h l i g h t a w o r d o r s e n t e n c e. l i c k o n t h e S t r i k e t h r o u g h ( D e l ) i c o n i n t h e A n n o t a t i o n s s e c t i o n. p e t h e r e p l a c e m e n t t e x t i n t o t h e b l u e b o x t h a t T y a p p e a r s. i g h l i g h t s t e x t i n e l l o w a n d o p e n s u p a t e x t b o x w h e r e c o m m e n t s c a n b e e n t e r e d. M a r k s a p o i n t i n t h e p r o o f w h e r e a c o m m e n t n e e d s t o b e h i g h l i g h t e d. i g h l i g h t t h e r e l e v a n t s e c t i o n o f t e x t. l i c k o n t h e A d d n o t e t o t e x t i c o n i n t h e A n n o t a t i o n s s e c t i o n. p e i n s t r u c t i o n o n w h a t s h o u l d b e c h a n g e d T y r e g a r d i n g t h e t e x t i n t o t h e e l l o w b o x t h a t a p p e a r s. l i c k o n t h e A d d s t i c k A n n o t a t i o n s s e c t i o n. n o t e i c o n i n t h e l i c k a t t h e p o i n t i n t h e p r o o f w h e r e t h e c o m m e n t s h o u l d b e i n s e r t e d. p e t h e c o m m e n t i n t o t h e T y a p p e a r s. e l l o w b o x t h a t

26 C C S S C C C C S C I n s e r t s a n i c o n l i n k i n g t o t h e a t t a c h e d f i l e i n t h e a p p r o p r i a t e p a c e i n t h e t e x t. I n s e r t s a s e l e c t e d s t a m p o n t o a n a p p r o p r i a t e p l a c e i n t h e p r o o f. l i c k o n t h e A t t a c h F i l e i c o n i n t h e A n n o t a t i o n s s e c t i o n. l i c k o n t h e A d d s t a m p i c o n i n t h e A n n o t a t i o n s s e c t i o n. l i c k o n t h e p r o o f t o w h e r e y o u d l i k e t h e a t t a c h e d f i l e t o b e l i n k e d. e l e c t t h e f i l e t o b e a t t a c h e d f r o m y o u r c o m p u t e r o r n e t w o r k. e l e c t t h e c o l o u r a n d t y p e o f i c o n t h a t w i l l a p p e a r i n t h e p r o o f. l i c k O K. e l e c t t h e s t a m p y o u w a n t t o u s e. ( T h e A p p r o v e d s t a m p i s u s u a l l y a v a i l a b l e d i r e c t l y i n t h e m e n u t h a t a p p e a r s ). l i c k o n t h e p r o o f w h e r e y o u d l i k e t h e s t a m p t o a p p e a r. ( W h e r e a p r o o f i s t o b e a p p r o v e d a s i t i s, t h i s w o u l d n o r m a l l y b e o n t h e f i r s t p a g e ). A l l o w s s h a p e s, l i n e s a n d f r e e f o r m a n n o t a t i o n s t o b e d r a w n o n p r o o f s a n d f o r c o m m e n t t o b e m a d e o n t h e s e m a r k s.. l i c k o n o n e o f t h e s h a p e s i n t h e D r a w i n g M a r k u p s s e c t i o n. l i c k o n t h e p r o o f a t t h e r e l e v a n t p o i n t a n d d r a w t h e s e l e c t e d s h a p e w i t h t h e c u r s o r. T o a d d a c o m m e n t t o t h e d r a w n s h a p e, m o v e t h e c u r s o r o v e r t h e s h a p e u n t i l a n a r r o w h e a d a p p e a r s. D o u b l e c l i c k o n t h e s h a p e a n d t y p e a n y t e x t i n t h e r e d b o x t h a t a p p e a r s.