Robert MacLaren, PharmD, BSc (Pharm), FCCM, FCCP Associate Professor School of Pharmacy

1. A Case-Based Approach Focusing on Nutrition and Sham Feeding for Managing Postoperative Ileus Robert MacLaren, PharmD, BSc (Pharm), FCCM, FCCP Associate Professor School of Pharmacy University of Colorado Critical Care Pharmacy Specialist University of Colorado Hospital Aurora, Colorado

2. Faculty Disclosure It is the policy of The France Foundation to ensure balance, independence, objectivity, and scientific rigor in all its sponsored educational activities. All faculty, activity planners, content reviewers, and staff participating in this activity will disclose to the participants any significant financial interest or other relationship with manufacturer(s) of any commercial product(s)/device(s) and/or provider(s) of commercial services included in this educational activity. The intent of this disclosure is not to prevent a person with a relevant financial or other relationship from participating in the activity, but rather to provide participants with information on which they can base their own judgments. The France Foundation has identified and resolved any and all conflicts of interest prior to the release of this activity. Dr. MacLaren has received grants/research support from Hospira.

3. Educational Learning Objectives Describe the importance of improving time to gastrointestinal recovery that occurs postsurgery and consider how this affects length of hospital stay and overall quality of patient care Evaluate the evidence for therapeutic options that may improve gastrointestinal recovery postsurgery and integrate these efforts toward supporting overall surgical quality measures Describe how interprofessional collaboration surrounding gastrointestinal surgery can result in better alignment with current surgical quality measures and formulate strategies to integrate this into current practice

4. Patient Case Goals Evaluate the evidence regarding the use of preoperative therapies, nasogastric tubes, enteral nutrition, and sham feeding for the management of postoperative ileus (POI) Describe how to use these modalities to manage POI and improve time to bowel recovery Given a case scenario, implement therapeutic strategies using these modalities to improve time to bowel recovery and patient outcomes

5. Patient Case RR is a 44-year-old female (5’5”, 70 kg) with known diverticulosis who is admitted with rectal bleeding She was discharged two weeks ago after one week of hospitalization for diverticulitis for which she received antibiotic therapy (levofloxacin 500 mg IV/PO daily and metronidazole 500 mg IV/PO tid); an abdominal computerized tomography scan at the time revealed diverticulitis of the sigmoid colon with no abscesses Her physical exam is normal, vital signs are within normal limits except heart rate of 100-120s, and all laboratory values are within normal limits except hemoglobin = 10 g/dL and hematocrit = 31.5 (values of both at prior discharge were 14 g/dL and 42, respectively) The anemia is believed related to bleeding diverticulosis and her stools are guaiac-positive Her past medical history is significant for hypothyroidism (levothyroxine 0.75 mg PO daily) and diverticulosis with a single attack two years prior RR does not smoke, rarely drinks alcohol, and her family history is noncontributory

6. Patient Case (cont) In the emergency room, RR is administered normal saline (2 L) and two units of packed red blood cells that result in hemoglobin and hematocrit values of 11 g/dL and 33, respectively A colonoscopy is performed that reveals a brisk bleed from diverticulosis of the sigmoid colon; local epinephrine is injected but blood continues to ooze The surgery team is consulted and the decision is to monitor her and only perform surgery if she requires additional blood products Levofloxacin 500 mg IV daily and metronidazole 500 mg IV tid are initiated She is preemptively administered a preoperative bowel preparation (Fleet's Phospho-soda solution 45 mL PO q 12 hours x 2) Over the course of the next 12 hours, RR requires two additional units of red blood cells The surgical team decides to perform a laparoscopic sigmoid resection In preparation for surgery, RR receives metoprolol 2.5 mg IV x 1, lorazepam 1 mg IV x 1, and vancomycin 1 g IV x 1

7. Do bowel preparation or anxiolytic prophylaxis before colorectal surgery reduce gastrointestinal dysfunction?

8. Preoperative Measures • Bowel Preparation • Cornerstone of colonic surgery for decades with primary purpose of reducing the concentration of colonic intraluminal bacteria • Meta-analysis (13 studies, N = 4777 patients): • Use of bowel preparation before colorectal surgery did not reduce anastomotic leakage (OR = 1.26, 95% CI 0.94-1.69) or wound infection (OR = 1.19, 95% CI = 0.98-1.45) • Should NOT be routine therapy, especially in urgent situations • Oral Carbohydrate Loading • Preoperative ORAL administration of glucose containing fluids reduces postoperative insulin resistance, catabolic response, and may hasten GI recovery and shorten hospital stay BUT keep normoglycemia Guenaga KK, et al. Cochrane Database Syst Rev. 2009;Jan21(1):CD001544. Story S, et al. Dig Surg. 2009;26:265-275. White PF, et al. Anesth Analg. 2007;104:1380-1396.

9. Preoperative Measures (cont) • Premedication • Anxiolytic agents (benzodiazepines) and antinausea medications reduce sympathetic-related complications and catabolic response and may facilitate GI recovery • Clonidine and β-blockers reduce intraoperative hemodynamic fluctuations AND have analgesia-sparing properties while optimizing analgesia • Randomized, double-blind study of 29 colorectal cases showed propranolol 4 mg i.v. every 12 hr starting 30 min before surgery reduced time to first bowel movement (82 ± 11 vs. 110 ± 9 hr, P < 0.01) Hallerback B, et al. Scand J Gastroenterol. 1987;22:149-155.

10. Preoperative Measures Conclusion: The preoperative practices of bowel preparation and NPO are not supported by data; preoperatively reducing the stress response with anxiolytics and/or β-blockers may hasten GI recovery

11. Patient Case (cont) Intraoperatively, RR is sedated with fentanyl and propofol During surgery, the laparoscopic sigmoid resection removes 10 cm of colon, including bleeding diverticulosis, and a colo-colonic anastomosis is performed Estimated blood loss is minimal and RR remains hemodynamically stable during the two-hour surgery In the PACU, the nasogastric tube is removed and she is transferred to the step-down unit for monitoring Transfer orders include bisacodyl 10 mg po tid, hydromorphone 1-2 mg PO qid PRN, ibuprofen 600 mg PO qid, liquid diet as tolerated, ambulate as tolerated PACU: post anesthesia care unit

12. Are there advantages to removing the NG tube immediately following surgery?

13. Prophylactic Nasogastric Decompression Following Abdominal Surgery • NG tubes traditionally used to decrease gastric retention in an effort to reduce functional burden on GI tract and limit aspiration risk

14. Prophylactic Nasogastric Decompression Following Abdominal Surgery • Meta-analysis • 33 Studies, N = 5,240 patients • Patients without routine NG tube use had: • Earlier return of bowel function by 0.52 days (P < 0.00001) • Decrease in pulmonary complications (P = 0.01) • Trend toward increase risk of wound infection (P = 0.22) • Shorter length of stay by 1.21 days • No difference in anastomotic leak between patients with vs without NG tubes (P = 0.70) • “Routine nasogastric decompression does not accomplish any of its intended goals and should be abandoned in favor of selective use of the nasogastric tube” Nelson R, et al. Cochrane Database Syst Rev. 2007;Jul 18(3):CD004929.

15. Prophylactic Nasogastric Decompression Following Abdominal Surgery Conclusion: NG tubes offer no benefit in most patients after abdominal surgery, may predispose patients to infectious complications, and should be removed quickly after surgery

16. Patient Case (cont) Postsurgery day 1 Hemoglobin and hematocrit are stable at 12 g/dL and 37, respectively RR is extremely nauseated and unable to eat despite ondansetron 8 mg IV tid, promethazine 25 mg IV x 2, and metoclopramide 10 mg IV x 1 Pain scores are 1-2/10 and she has only required hydromorphone 1 mg PO x 1 She is ambulating with difficulty due to feeling nauseated The care team orders one stick of gum qid x 15 minutes

17. Why order chewing gum?

18. Gum Chewing (Sham Feeding) • Stimulates GI motility by eliciting reflex response and stimulating release of hormonal factors, but may be related to sorbitol content

19. Gum Chewing (Sham Feeding)

20. Gum Chewing (Sham Feeding) Conclusion: Gum chewing appears effective for expediting GI recovery, especially in the absence of adequate oral nutritional intake

21. Patient Case (cont) Postsurgery day 2 RR remains hemodynamically stable Her nausea is slightly improved and she is able to partially tolerate a soft diet (eg, Jell-O®) in small portions She continues to receive antinausea medications RR is unable to advance her diet despite ondansetron 8 mg IV tid, promethazine 25 mg IV x 3, and metoclopramide 10 mg IV x 1 Pain scores are 1-2/10 with no additional use of hydromorphone Flatus is present but bowel movements are absent She is able to ambulate The care team orders a small-bore nasogastric tube for enteral nutrition supplementation

22. Is early enteral nutrition appropriate for this patient?

23. Early Oral/Enteral Nutrition Within 24 Hours of Intestinal Surgery • Traditionally patients were kept NPO to “rest the GI tract” and allow healing after surgery • Mechanism of action of early enteral nutrition: maintains gut barrier function and lymphoid tissue; promotes mucus, bile, IgA secretion; and maintains peristalsis and blood flow

24. Early Oral/Enteral Nutrition Within 24 Hours of Intestinal Surgery • Meta-analysis of 13 clinical trials, N = 1,173 patients • Mortality – reduced with early post-op feeding • RR (95% CI): 0.41 (0.18, 0.93) • Data suggestive of reduced • Wound Infections – RR (95% CI): 0.77 (0.48, 1.22) • Pneumonia - RR (95% CI): 0.76 (0.36, 1.58) • Length of Stay - RR (95% CI): -0.60 (-0.66, -0.54) • Anastomotic dehiscence – little evidence of benefit or harm • RR (95% CI): 0.69 (0.36, 1.32) • Overall conclusion: no benefit for restricting postoperative oral/enteral nutrition Lewis S, et al. J Gastrointest Surg. 2009;13:569-575.

25. Early Oral/Enteral Nutrition Within 24 Hours of Intestinal Surgery Conclusion: Enteral nutrition support may reduce complications and morbidity when initiated early after intestinal surgery

26. Case Summary • Postsurgery days 3-4 • The nausea dissipates and RR is able to eat a regular diet • Supplemental enteral nutrition support is discontinued • Levothyroxine 0.75 mg PO daily is started • Ondansetron 4 mg PO tid is continued while promethazine and metoclopramide are discontinued • Ibuprofen and bisacodyl are discontinued • Bowel movement occurs on day 4 • Pain scores are 0-1/10 • RR remains hemodynamically stable • Postsurgery day 5: RR is discharged

27. Summary • Standards of practice for intestinal surgery should NOT include the routine use of regimens for preoperative bowel preparation • Preoperative enteral administration of glucose containing fluids before surgery may expedite GI recovery, but further investigations are needed • Preoperatively reducing the stress response of surgery with anxiolytics and/or β-blockers may hasten GI recovery and should be considered in hemodynamically stable patients • Nasogastric tubes offer no benefit in most patients after abdominal surgery and should be removed quickly • Nasogastric tubes may expose patients to greater risk of pulmonary complications (eg, pneumonia) • Enteral nutrition should be started within 24 hours of abdominal surgery as it reduces the rate of complications and improves outcomes without safety concerns • Sham feeding, in particular gum chewing, expedites GI recovery • It may be considered in all patients after abdominal surgery, but definitely should be implemented in patients unable to eat • May be implemented preoperatively • Limited data supporting other modes of sham feeding (eg, candy sucking, ice chips) • A multimodal approach for managing POI should consider incorporating appropriate preoperative management, rapid removal of nasogastric tubes, and early enteral nutrition and/or sham feeding