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

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. Faculty Disclosure

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

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

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

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 Patient Case – Intraoperative Anesthesia

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

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) Patient Case – Intraoperative Monitoring

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% 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 Patient Case – Fluid Management

Pharmacology of Starch Classification Molecular Weight (kDal) Degree of Substitution Examples High MW> Hespan™ Hextend™ Medium MW 200–2800.5Elo-HAES™ HAES-steril™ Pentalyte™ Low MW70–1300.4Voluven ® Westphal M, et al. Anesthesiol. 2009;111: Boldt J, Suttner S. Minerva Anesthesiol. 2005;71:

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 to maintain adequate levels of anesthesia Patient Case – Fluid Management SVV: stroke volume variation

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

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

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/m 2 using FloTrac monitor Primary outcome: length of stay (LOS) Mayer J, et al. Critical Care. 2010;14:R18.

Goal-directed Fluid Therapy With FloTrac Stroke Volume Variation Standard N = 30 GDT N = 30 Pvalue LOS (Days)19 ( ) 15 ( ) Complications15 (50%)6 (20%)0.03 Dobutamine (mcg/kg/h) 4.1 ± ± Colloid (mL)817 ± ± Mayer J, et al. Critical Care. 2010;14:R18.

Noblett SE, et al. Br J Surg. 2006;93: Goal-directed Fluid Management *median (interquartile range) ‡ Mann-Whitney U test/Χ 2 test/Fisher’s exact test † Mean (standard deviation)

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

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

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

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

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

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

Goal-directed Fluid Therapy Length of Stay WMD (-4.22, -1.66) P < Bundgaard-Nielsen M, et al. Acta Anaesthesiol Scand. 2007;51:

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

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

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

n = 10 IV Fluid and Salt Restriction 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 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: ) and 52 min (95% CI: 9-95), n = 10 P = Standard groupRestricted group Solid Phase Gastric Emptying Time (T50 min) n = 10 P = Standard groupRestricted group Liquid Phase Gastric Emptying Time (T50 min) Lobo DN, et al. Lancet. 2002;359: MOA = mechanism of action

IV Fluid and Salt Restriction Standard Salt and Fluid Restriction Pvalue Flatus Stool Length of Stay Complications Lobo DN, et al. Lancet. 2002;359: 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.

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

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

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 Fluid Management – Crystalloids

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

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