2 nd IFAD, Antwerpen 2012

1. Fluid strategy in the perioperative setting IS MORE, OR LESS, BETTER? Azriel Perel Professor and Chairman Department of Anesthesiology and Intensive Care Sheba Medical Center, Tel Aviv University Israel 2nd IFAD, Antwerpen 2012

2. Disclosure The speaker cooperates with the following companies BMEYE FlowSense iMDsoft Pulsion perelao@shani.net

3. The mortality rate for patients undergoing non-cardiac surgery is higher than anticipated. • There is a need for strategies to improve care for this group of patients.

4. Perioperative goal-directed therapy (GDT) improves outcome

5. The use of a preemptive strategy of hemodynamic monitoring and coupled therapy reduces surgical mortality and morbidity.

6. Short-term peri-operative GDT may improve long-term outcomes, in part due to its ability to reduce the number of perioperative complications.

7. Gurgel ST et al. Anesthesia Analgesia 2011

8. GDT – the ‘basic’ technique • A bolus of 200 ml colloid is administered over 2 min, and 5 min later the stroke volume (SV) is assessed. • The procedure is repeated if there was an increase in SV of >10%. • When the fluid bolus does not result in a SV increment >10%, optimization is regarded as achieved.

9. Fluids should be given to increase CO, and inodilators added once the patient is no longer fluid (preload) responsive or not achieving the following goals: • CI > 4.5 L/min/m2 • DO2I ≥ 600 ml/min/m2

10. “It may be considered unethical not to use goal-directed perioperative therapy”

11. “We believe that a minimally invasive cardiac output monitor should be considered in all major surgery to optimize preload.”

12. The oesophageal Doppler monitor ‘‘should be considered for use in patients undergoing major or high-risk surgery…(since its use is associated with) a reduction in post-operative complications, use of central venous catheters and in-hospital stay…The cost saving per patient…is about £1100 based on a 7.5-day hospital stay.’’

13. What hemodynamic monitoring do you routinely use for the management of high-risk surgery patients?

14. Cannesson and colleagues show us that practice remains out of sync with the current evidence base with regards to GDT. • Whether this is because physicians still doubt the evidence base, worry about inaccuracies in monitoring techniques or simply lack the energy and motivation needed to change practice is unclear.

15. The mechanisms underlying the reported benefit of GDT remain uncertain

16. The rationale of perioperative GDT • Major surgery generates a strong systemic inflammatory response and an overall substantial increase in oxygen demand, which is normally met by an increase in cardiac output (CO) and in oxygen extraction. • Patients that do not have the physiological reserve to increase the CO to the required level may have inadequate tissue perfusion and therefore be at higher risk for postoperative complications.

18. Postoperative fluid therapy, guided by SV + low-dose dopexamine, was associated with improved sublingual and cutaneous microvascular flow. • However, this improvement was not associated with differences in inflammatory markers or in overall complication rate.

19. There is an urgent need to evaluate the pathophysiological mechanisms that are responsible for the positive results reported by most clinical GDT studies.

20. In most studies GDT was performed in the intraoperative period and in some within the very early postoperative period. • When to institute GDT needs to be clarified.

22. British consensus guidelines on intravenous fluid therapy for adult surgical patients. 2011. Powell-Tuck J, et al. www.bapen.org.uk/pdfs/bapen_pubs/giftasup.pdf. “Concern arose from a high incidence of post-operative sodium and water overload, and evidence to suggest that preventing or treating this, by more accurate fluid therapy, would improve outcome.

23. British consensus guidelines on intravenous fluid therapy for adult surgical patients. 2011. Powell-Tuck J, et al. www.bapen.org.uk/pdfs/bapen_pubs/giftasup.pdf.

24. The evidence behind GDT is still being questioned

25. Despite the apparent improvements in postoperative outcome by the GDT concept all studies have problems in their design.

26. The evidence underpinning ODM-guided fluid administration has not been critically appraised despite quantitative meta-analyses. • The observed initial clinical benefits may be largely offset by recent advances in surgical techniques and peri-operative care.

27. There are distinct challenges associated with the design and conduct of GDT trials which are not easily solved. The findings of all previous GDT trials must be interpreted in the context of the design choices that the investigators have made. • Blinding is an important potential source of bias in GDT trials and small GDT trials in particular are vulnerable to bias. • The lack of confirmation in large trials is a significant limitation of the evidence base for GDT.

28. Fluid management for laparoscopic colectomy: a prospective, randomized assessment of goal-directed administration of balanced salt solution or hetastarch coupled with an enhanced recovery program. Senagore AJ, et al. Dis Colon Rectum. 2009 ;52:1935 • A double-blinded, prospective, randomized study in patients undergoing laparoscopic colectomy, who received standard care, GDT with hetastarch, or GDT with lactated Ringer's. • The hetastarch group had the longest hospital stay. • Goal-directed fluid management with a colloid solution offers no advantage and is more costly.

29. Intraoperative SV optimization conferred no additional benefit over standard fluid therapy. • In an aerobically fit subgroup of patients, GDT was associated with detrimental effects on the primary outcome. • GDT focusing on SV maximization may have important limitations including a risk of iatrogenic fluid overload which may be associated with prolonged hospital stay.

30. Anesth Analg 2011;112:130–8 The routine use of dopexamine does not confer an additional clinical benefit.

31. Ghosh S, Arthur B, Klein AA • When reading the clinical trials relating to use of the esophageal Doppler, it is striking that the prime intervention differentiating controls from study group patients is the infusion of about 500 ml colloid intraoperatively. • Can it really be that a monitoring device used for up to four hours out of an eight-day hospital stay, and the infusion of a small bag of fluid, can save the NHS £1100 per patient? • If so, why not just adopt a less conservative approach to intra-operative fluid balance and dispense with the monitoring device as well?

32. Can GDT lead to detrimental fluid overload?

35. Cecconi M et al Cecconi M et al

36. Patients undergoing major abdominal surgery underwent pre-operative fluid loading with 25 ml/kg of Ringer’s solution in the six hours before surgery. • Pre-operative intravenous fluid loading leads to a non-significant reduction in hospital length of stay after high-risk major surgery and is likely to be cost-effective.

37. Kudsk KA, Ann Surg 2003; 238:649 (editorial) “We have to re-examine whether we have indeed started to underestimate the effects of fluid overload even in patients undergoing medium-risk surgery… ….IV fluids, the most commonly used drug in the hospital, are a double-edged sword.”

38. Blood volume after fasting is normal, and a fluid-consuming third space has never been reliably shown. • The endothelial glycocalyx plays a key role and is destroyed not only by ischemia and surgery, but also by acute hypervolemia. • Undifferentiated fluid handling may increase the shift toward the interstitial space.

39. Avoiding hypervolemia plays a pivotal role when treating patients both perioperatively and in the ICU.

40. In patients undergoing elective intra-abdominal surgery, intraoperative use of restrictive fluid management may be advantageous because it reduces postoperative morbidity and shortens hospital stay.

41. Crit Care Med 1990; 18:728 • Patients who had >20% weight gain had more vasopressor dependence and higher mortality. • The morbidity of fluid overload can be significant and warrants a fresh look at the methods of intraoperative fluid resuscitation.

42. Both fluid overload and changes in serum creatinine are independent prognostic markers after cardiac surgery. • Fluid overload was the variable most related length of stay in the ICU.

43. National Confidential Enquiry into Patient Outcome and Death. 1999 Report: Extremes of Age. http://www.ncepod.org.uk • National Confidential Enquiry into Perioperative Death have highlighted over-hydration as a contributory cause in the genesis of postoperative problems leading to death. • Carefully considered case histories have led to specific recommendations regarding careful fluid management (the implication being restriction) in vulnerable patients and those most at risk, such as the elderly.

45. A reductions in SV of >10% as measured by the E-Doppler has a sensitivity of only 37% in identifying fluid responsiveness, and therefore may be related to other factors aside from preload.

46. The 24 studies included 803 patients. Overall, 56 ± 16% of the patients responded to a fluid challenge.

49. Should optimization to supra-normal values be done in all patients?

50. Prospective trial of supra-normal values of survivors as therapeutic goals in high-risk surgical patients Shoemaker WC, et al. Chest 1988; 94: 1176 A randomized clinical trial of the effect of deliberate perioperative increase of oxygen delivery on mortality in high-risk surgical patients Boyd O, Grounds RM, Bennett ED. JAMA 1993;270:2699