Fluid Management

1. Fluid Management Tong Joo (TJ) Gan, MD, FRCA, FFARCS(I) Professor of Anesthesiology Vice Chairman Clinical Research Duke University Medical Center Durham, North Carolina

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. Gan has received grants/research support from Acacia, Baxter, Durect, Eisai, and NICOM. He has received honoraria from Baxter, Eisai, Fresenius, Hospira, and Xanodyne.

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 • 68-year-old female, 100 kg, admitted for partial open colectomy • Past medical history • Known cardiac risk factors • Insulin-dependent diabetes mellitus • Hypertension • Vasculitis

5. Patient Case – Anesthetic Plan • General anesthesia • Fentanyl 100 mcg and midazolam 2 mg premedication • Celecoxib 400 mg • Induction with propofol • Intubated with succinylcholine • Muscle relaxation maintained with cisatracurium

6. Patient Case – Intraoperative Anesthesia • Anesthesia maintained with sevoflurane, air and oxygen • Continuous infusion of fentanyl 0.03 mcg/kg/min • Forced air warming using Bair Hugger® temperature management system

7. Potential Benefits of Cardiac Output and Stroke Volume Monitoring • Monitor intraoperative dynamic hemodynamic parameters • Optimize fluid status • Avoid long period of hypovolemia • Avoid excess fluid administration • Identify causes of low urine output

8. Patient Case – Intraoperative Monitoring • Heart rate • Indirect blood pressure • Continuous ECG • Arterial line • 2–16 G peripheral intravenous catheters • Urinary catheter for measuring urine output • Continuous arterial wave cardiac output (FloTrac system – flow-based hemodynamic monitoring)

9. Patient Case – Fluid Management • 500 mL fluid bolus in the preop holding area to rehydrate following bowel prep • Continuous infusion of lactated Ringer’s solution at 4 ml/kg/h • Goal directed fluid management using A-line minimally invasive cardiac output monitoring to target stroke volume variation (SVV) < 13%

10. Patient Case – Fluid Management • Colloid • Voluven® administered at 250 mL aliquots to keep stroke volume variation < 13% • Variety of hydroxyethyl starch • Newer generation with lower molecular weight (eg, Voluven®) associated with less coagulation disturbances • Continuous cardiac output monitoring with FloTrac system

11. Pharmacology of Starch Molecular Degree of Examples Classification Weight Substitution (kDal) High MW > 450 0.7 Hespan™ Hextend™ 200– 280 0.5 Elo - HAES™ Medium MW HAES - steril ™ Pentalyte ™ Low MW 70– 130 0.4 Voluven® Westphal M, et al. Anesthesiol. 2009;111:187-202. Boldt J, Suttner S. Minerva Anesthesiol. 2005;71:741-758.

12. Patient Case – Fluid Management • Patient received 5 boluses of Voluven® 250 mL each when SVV > 13% • Urine output averaged 50 mL/hr • BP maintained within 130/75 mm Hg, HR 83/min • Bispectral index between 50-60 to maintain adequate levels of anesthesia SVV: stroke volume variation

13. SVV = 8 SVV = 8 SVV = 12 SVV = 15 SVV = 17 SVV = 16 250 mL Voluven® fluid challenge

14. Does perioperative goal-directed fluid therapy impact postoperative bowel function or length of stay? Perioperative Goal-directed Therapy

15. Goal-directed Fluid Therapy (GDT) – FloTrac-driven Goals • Single center, prospective, randomized trial • 60 high-risk patients for major abdominal surgery • Control group (standard management) • MAP between 65–90 mm Hg • CVP between 8–12 mm Hg • Urine output > 0.5 mL/kg/h • GDT group (cardiac index-based intraoperative optimization protocol) • Cardiac index > 2.5 L/min/m2 using FloTrac monitor • Primary outcome: length of stay (LOS) Mayer J, et al. Critical Care. 2010;14:R18.

16. Standard GDT P value N = 30 N = 30 LOS (Days) 19 15 0.006 (14 - 23.5) (12 - 17.75) Complications 15 (50%) 6 (20%) 0.03 ± ± Dobutamine 4.1 19 30.4 50.5 0.01 (mcg/kg/h) ± ± Colloid ( mL ) 817 467 1188 550 0.006 Goal-directed Fluid Therapy With FloTrac Stroke Volume Variation Mayer J, et al. Critical Care. 2010;14:R18.

17. Goal-directed Fluid Management *median (interquartile range) ‡Mann-Whitney U test/Χ2 test/Fisher’s exact test †Mean (standard deviation) Noblett SE, et al. Br J Surg. 2006;93:1069-1076.

18. Goal-directed Fluid Therapy Gan TJ, et al. Anesthesiology. 2002;97:820-826.

19. Goal-directed Fluid Therapy • Numerous studies have demonstrated goal-directed fluid therapy improves bowel function and shortens hospital length of stay

20. Goal-directed Fluid Therapy • Recent meta-analyses demonstrated goal- directed fluid therapy reduces major and minor gastrointestinal dysfunction

21. Goal-directed Fluid Therapy Meta-analysis of Randomized Controlled Trials Giglio MT, et al. Br J Anaesth. 2009;103:637-646.

22. Goal-directed Fluid Therapy Meta-analysis of Randomized Controlled Trials Giglio MT, et al. Br J Anaesth. 2009;103:637-646.

23. Goal-directed Fluid Therapy Systematic Review Hospital Length of Stay Complications Abbas SM, et al. Anaesthesia. 2008;63:44-51.

24. Goal-directed Fluid TherapyLength of Stay WMD -2.94 (-4.22, -1.66) P < 0.00001 Bundgaard-Nielsen M, et al. Acta Anaesthesiol Scand. 2007;51:331-340.

25. Fluid Management – Crystalloids Does excess crystalloid administration improve postoperative bowel recovery?

26. Volume of Crystalloids and Weight Gain Chappell D, et al. Anesthesiology. 2008;109:723-740.

27. Colloids vs CrystalloidsPatients Undergoing Major Elective Noncardiac Surgery % of patients *P < 0.05 * * * Moretti E, et al. Anesth Analg. 2003;96:611-617. LR: lactated Ringer’s solution

28. IV Fluid and Salt Restriction 250 200 150 100 50 0 Solid Phase Gastric Emptying Time(T50 min) n = 10 Solid lines are medians, shaded areas IQRs, and whiskers extreme values Differences between medians for solid and liquid phase T50 were 56 min (95% CI: 12-132) and 52 min (95% CI: 9-95), n = 10 • MOA: salt/water restriction improves canine gastric emptying time • Lobo compared standard (≥ 3L/D fluids; 154 mmol Na+) with restricted (≤ 2L/D fluids; 77 mmol Na+) protocols after open hemicolectomy • Significantly more complications in standard treatment group P = 0.028 Standard group Restricted group 200 150 100 50 0 Liquid Phase Gastric Emptying Time(T50 min) n = 10 n = 10 P = 0.017 Standard group Restricted group MOA = mechanism of action Lobo DN, et al. Lancet. 2002;359:1812-1818.

29. Salt and Standard P value Fluid Restriction Flatus 4 3 0.001 Stool 6.5 4 0.001 Length of Stay 9 6 0.001 Complications 7 1 0.01 IV Fluid and Salt Restriction Positive salt and water balance causing a weight gain of 3 kg following elective colonic resection is associated with delayed recovery of GI function, increased complication rate, and increased length of stay. Lobo DN, et al. Lancet. 2002;359:1812-1818.

30. Elective intraabdominal surgery • Crystalloid: lactated ringers • Randomized into 2 groups • Liberal fluid regimen: 10 ml/kg and 12 ml/kg/h • Restricted regimen: 4 ml/kg/h • Primary outcome: death or complications

31. Liberal Group Restrictive Group ± Intraoperative volume received (mL) 3878 ± 1170 1408 946* Patients with 31% 17%** complications Time to bowel 6 (4-9) 4 (3 - 9)* movement (days) Hospital stay 9 (7-24) 8 (6 - 21)† (days) *P < 0.001; **P < 0.05; †P = 0.01

32. Fluid Management – Crystalloids • Excess crystalloid (in particular excess salt and water) administration has been associated with weight gain and postoperative bowel dysfunction. Delay in bowel recovery translates into delay in hospital discharge

33. Patient Case – Hospital Course • Patient’s pain was well-controlled with PCA fentanyl • Postoperative Day 3: patient tolerating semi solid, NG tube removed; PCA discontinued, patient treated with ibuprofen and Vicodin® PRN • Postoperative Day 4: advanced to solid diet, tolerated well, full bowel function established, started ambulation • Postoperative Day 5: hospital discharge

34. Summary • Fluid management plays an important role in the postoperative outcome and bowel function • Goal-directed fluid administration promotes earlier bowel function and shorten length of stay • Avoiding crystalloid excess is associated with earlier return to bowel function