1. PEN Group Nutritional Support – A vision for the future Fast Track approach to recovery after surgery August 2005 John MacFie MD FRCS

2. Hospital Stay After Colonic Surgery 1990 Days Multimodal Laparoscopic Conventional

3. Fast Track Surgery Kehlet H and Wilmore DW Br J Surg 2005 ; 92 : 3-4

4. Problems: Observational studies only Other perioperative factors not considered

6. Optimisation Programme: Scabro Preoperative information Hathaway 1986 (n=4018) No bowel preparation Brownson 1992, Burke 1994, Santos 1994, Platell 1998, Miettinen 2000 (n>400) Synbiotics McNaught/Woodcock 2001 (n=129) Preoperative carbohydrates Nygren 1996, Ljungqvist 2001 (n=52) Transverse incision Armstrong 1990 (n=60), Lindgren 2001 (n=53)

7. Optimisation Programme: Scabro Perioperative Oxygen Grief 2000 (n=500) No nasogastric tubes/drains MacFie 1993 (n=148) Epidural analgesia/ no opiates Carli 2001 (n=42), Rodgers 2000 (n=9559) Exercise programme Henricksen 2002 (n=40) Early resumption oral diet Reissman 1995 (n=161), Lewis 2001 (n=837)

8. Preoperative bowel preparation General Anaesthesia Surgeons choice - Incision - Drain - Nasogastric tube Patient controlled analgesia Ward mobilization !Traditional fluid regimen! Conventional treatment :

9. Anderson ADG, Mc Naught CE, MacFie J, et al. Randomized clinical trial of multimodal optimisation and standard perioperative surgical care. BJS 2003; 90: 1497-1504 Patients: right and left hemicolectomy only self caring / independent / on telephone Methods: 10 point optimisation programme Results: optimisation associated with - Lower fatigue scores - Maintained grip strength - Lower pain scores

10. Anderson ADG, Mc Naught CE, MacFie J, et al. Randomized clinical trial of multimodal optimisation and standard perioperative surgical care. BJS 2003; 90: 1497-1504 Length of stay (days) Control Optimisation Group N = 11 14 p = 0.002 Primary outcome: Primary outcome: - Shortened hospital stay (median 3 vs. 7 days) Optimisation is safe Optimisation is safe Probably multifactorial Probably multifactorial

11. Multi modal treatment strategies Problems with PRCTs: Unblinded Selected patients Overwhelming influence of epidurals

12. To assess the effect of a multimodal optimisation package (excluding epidural anaesthesia) on a consecutive series of patients (i.e. unselected) undergoing major colorectal resections ScaBro Multimodal trial 2

13. Optimisation package Pre-operative Per-operative Post-operative cf previous study : major excisional surgery / all pts had epidurals - Written pre-op information. - Pre-assessment by SpR / Anaesthetist. - Synbiotics. - No bowel prep. - Oral carbohydrate loading & 3h fast. - High inspired O 2 (80%). - Transverse incision. - No drains or post-op NGT. - Early fluid & diet reintroduction. - Structured mobilisation plan. - No opiate analgesics.

14. End points Physiological:Spirometry, grip strength, POSSUM, duration of catheterisation, time to mobilisation. Psychological:Cognitive function scoring, fatigue scoring, pain scoring, analgesic requirements. Gut function:Tolerance to fluids, fluid balance, tolerance to diet, duration of IV fluids. Outcome:Length of stay, complications, need for readmission, GP visits.

15. Design of study 39 consecutive patients needing major colonic surgery 39 consecutive patients needing major colonic surgery RandomisationRandomisation Optimisation group (N = 19) Optimisation group (N = 19) Control group (N = 20) Control group (N = 20) Followed up for 30 days post-op

16. Patients Control groupOptimisation groupP - value Total number2019 Age (years) *67 NS Sex ratio (M : F)14 : 69 : 10NS Body mass index *2724NS ASA *22NS POSSUM score *3228NS * Values are median, NS (not significant)

17. Surgical procedures OperationControl groupOptimisation group R/L hemicolectomy75 Sigmoid colectomy / Hartmanns Anterior resection / Subtotal colectomy912 Panproctocolectomy / Pouch formation22 AP resection20 ControlOptimisationP value POSSUM operative severity *1213NS Malignancy1215NS * Values are median, NS (not significant)

18. Results 1: physiological function ControlOptimisationP – value Time out of bed on day 1 (minutes) 81050.047* Duration of catheterisation (hours) 72470.002* Values are median No difference in: - POSSUM scoring - POSSUM scoring - Grip strength - Grip strength - Spirometry - Spirometry - Time to full mobilisation - Time to full mobilisation

19. Results 2: psychological function No difference in: - Cognitive function scoring - Fatigue scoring - Pain scoring - Analgesic requirements

20. Results 3: gut function p = 0.007 N = 20 19 Control Optimisation Group Duration of IV fluids (hours) Duration of IV Fluids Return of Gut Function N = 20 19 Control Optimisation Group Return of Gut Function (hours) p = 0.042

21. Results 4: length of stay Control Optimisation Length of stay (days) Percentage (%) p = 0.027 N = 20 19 Control Optimisation Group aLength of stay (days)

22. Results 5: morbidity & mortality Control Optimisation P-value Complications 15 9 0.076 GP visits * 0 (0 - 1) 1 (0 - 1) 0.373 Readmissions 4 1 0.169 Deaths 0 1 0.299 * Values are median (interquartile range)

23. so, it appears that: Optimisation decreases: - time to mobilisation. - duration of catheterisation. - dependency on intravenous fluids. - length of hospital stay. Shortened stay had no observed effect on: - morbidity. - need for readmission. - GP visits. - mortality.

24. and that : Multimodal optimisation is safe & overall is superior to conventional care. This cannot be only because of epidural analgesia. ??? WHY

25. Why? reduced cardiovascular & immunological stress reduced insulin resistance reduced post-operative pain reduced catecholamine / cortisol response avoidance fluid overload less use of blood products 1 shorter hospital stay early return to full activity preservation / early return of gut function 1. Kiran RP et al. Arch Surg. 2004 Jan;139(1):39-42.

26. Optimisation package Pre-operative Per-operative Post-operative cf previous study : major excisional surgery / all pts had epidurals - Written pre-op information. - Pre-assessment by SpR / Anaesthetist. - Synbiotics. - No bowel prep. - Oral carbohydrate loading & 3h fast. - High inspired O 2 (80%). - Transverse incision. - No drains or post-op NGT. - Early fluid & diet reintroduction. - Structured mobilisation plan. - No opiate analgesics.

27. Optimisation package Pre-operative Per-operative Post-operative cf previous study : major excisional surgery / all pts had epidurals - Written pre-op information. - Pre-assessment by SpR / Anaesthetist. - Synbiotics. - No bowel prep. - Oral carbohydrate loading & 3h fast. - High inspired O 2 (80%). - Transverse incision. - No drains or post-op NGT. - Early fluid & diet reintroduction. - Structured mobilisation plan. - No opiate analgesics.

28. Meta-analysis: Early enteral feeding vs nil by mouth Lewis SJ et al. 2001 * *

29. Early vs delayed nutrient intake Heyland et al Canadian practice guidelines, JPEN 2003 27;355 8 RCTs (level 2) 8 RCTs (level 2) Early EN associated with trend towards mortality Early EN associated with trend towards mortality (RR 0.52; 95% CI 0.25 – 1.08, p=.08) Early EN associated with trend towards infections Early EN associated with trend towards infections (RR 0.66; 95% CI 0.36 – 1.22, p=.19)

30. The Enteral Nutrition Dilemma: >60% of patients fail to meet nutritional requirements. Vs. Gut should be used for feeding when possible.

31. N P Woodcock et al. Nutrition 2001; 17: 1-12 Enteral vs Parenteral Nutrition: a pragmatic study

32. Patients receiving less than 80% of target intake N P Woodcock et al. Nutrition 2001; 17: 1-12

33. Complications / causes of inadequate intake % incidence of complications N P Woodcock et al. Nutrition 2001; 17: 1-12 P < 0.001 p < 0.001 P = 0.02 p < 0.001

34. Overall mortality

35. Summary EN is associated with a significantly higher incidence of non- septic morbidity and mortality than TPN EN is associated with a significantly higher incidence of inadequate nutritional intake compared to TPN There is no significant difference between EN and TPN in the incidence of septic morbidity

36. Clinicians are poor are poor at assessing Intestinal function Inadequate gut function is a predictor of poor prognosis poor prognosis

37. Tolerance of enteral nutrition: A prognostic indicator? NS P<0.05 ABSI: Abbreviated burn severity index Raff T, Burns 1997;23:19-25

38. The gut is not just a digestive organ… antigenic sampling antigenic sampling maintains stable ecoflora maintains stable ecoflora essential barrier function essential barrier function largest producer of cytokines largest producer of cytokines

39. Early systemic hyperinflammation 3 - 5 days 10 - 14 days Delayed immumosuppression

40. Hypothetical timecourse of sepsis: Expression of pro- and anti-inflammatory cytokines Mayer et al. (1998) Curr. Opin. Clin. Nutr. Metab. Care 1, 179-184. TNF IL-1 IL-6 IL-8 IL-10 TGFb IL-13 IL-4 Sepsis- Induction Inflammation Hyper Hypo physiological Range These cytokines (TNF-, IL-1, IL-6, IL- 8) are largely, if not completely, responsible for the clinical signs and symptoms of the septic response to bacterial infection. Vervloet et al. (1998) Sem. Thromb. Hemostasis 24, 33-44

41. Pro-inflammatory cytokines TNF, IL1, IL6, IL8 Anti-inflammatory cytokines IL4, IL10 etc Optimal outcome Poor outcome, increased mortality The balance between pro-and anti-inflammatory cytokines is important

42. Splanchnic Hypoperfusion Gut Ischaemia-Reperfusion injury Loss of Gut Barrier Function Gut Inflammatory Response Gut derived inflammatory factors SIRS, ARDS, MODS 3 – Hit Model (De 3 – Hit Model (Deitch A. Surgery 2002,131:241) 1st 2nd 3rd

43. … when this works… USE IT! & dont abuse it

44. But what about paralytic ileus ? is uncommon is uncommon is not inevitable is not inevitable does not necessitate the routine use of post pyloric feeding or prokinetics does not necessitate the routine use of post pyloric feeding or prokinetics is not diagnosed using the stethescope!! is not diagnosed using the stethescope!!

45. Enteral Nutrition The origins of adjuvant feeding Adjuvant feeding ….… the Egyptian way

46. the method of feeding should be determined by gastrointestinal tolerance the method of feeding should be determined by gastrointestinal tolerance when there is reasonable doubt as to the adequacy of gastrointestinal function patients should receive when there is reasonable doubt as to the adequacy of gastrointestinal function patients should receive parenteral nutrition optimal nutritional support should comprise a optimal nutritional support should comprise a combination of both enteral and parenteral routes of delivery of delivery

47. Fast track surgery necessitates optimal nutritional support and this needs teamwork:

49. Fast Track Surgery Summary: It does work It is not entirely dependant on analgesia Our evidence suggests that maintainence of intestinal function is a critical factor