1. Dirk Himpe MD PhD MHE EDIC ZNA Middelheim General Hospital Antwerp Belgium The hypertonics: lessons from massive fluid administration for small volume therapy

2. .Hypertonics: harmless or not? – first title.I am not an expert in small volume therapy Disclosure statements

3. CPB: model massive fluid load

4. Bloodvolume Htc: Htc: 45 % 20-25 % start CPB (few minutes) CPB: model massive fluid load

5. Succinyl-linked GEL in buffered vehicle Albumin-Hartmann Himpe D. et al. JCTVA 1991, 5:457-66 Urea-linked GEL in NS Base Excess (mean ± 1.96 SEM)

6. Base EM. et al. JCTVA 2011, 25:407-14 Hydroxyethyl Starch 6% 130/0.4 in NS (Voluven) in NS (Voluven) Hydroxyethyl Starch 6% 130/0.4 in a Balanced Electrolyte Solution (Volulyte) in a Balanced Electrolyte Solution (Volulyte) Base Excess (mean ± SD)

7. Gel* Fluid engineering balanced colloids (*) Hayhoe et al. ICM 1999 Liskaser et al. Anesthesiology 2000 Himpe et al. BJA 2003 Liskaser et al. Anaesth Intensive Care 2009

8. Anesthesiology 2007; 106:132–43 Copyright © 2006, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc. Novel Starches Single-dose Pharmacokinetics and Effects on Blood Coagulation Caveh Madjdpour, M.D.,* Caroline Thyes, M.D.,* Thierry Buclin, M.D.,† Philippe Frascarolo, Ph.D.,‡ Ine` s von Roten, M.D.,* Andreas Fisch, Ph.D.,§ Marc Burmeister, M.D., Thomas Bombeli, M.D.,# Donat R. Spahn, M.D., F.R.C.A.** 106: 132-143, 2007 Negatively charged starches could, however, be formed through the linkage of carboxymethyl rather than hydroxyethyl groups to the starch backbone.

9. Outcome = Hitting the right target(s).acid-base status.right fluid load Goal Directed Therapy (GDT)

10. Lowell, CCM 1990 18:728, 1990 < 10 % 10-20 % > 20 % 020406080100 Mortality % Weight gain after cardiac surgery

11. Himpe D, AAB, 54:207-15, 2003

12. Surgery 1989, 105:65-71, 1989. Surgery (4): 7.8% in favour of colloids Trauma (4): 12.5% in favour of crystalloids

13. Leaky Capillaries …

14. Swelling RBC & Endothelial cells

15. Swelling RBC & Endothelial cells

16. Fluid shifts into the interstitial space: Type 1 – physiologic shift colloid-free fluid; Type 2 – dysfunction vascular barrier (endothelial glycocalyx capillary membrane):.surgical manipulation.reperfusion injury and inflammatory mediators.iatrogenic hypervolemia (less volume effect) Strunden M et al. Annals of Intensive Care 2011, 1:2 Chappel D et al. Anesthesiology 2008; 109:723–40 Microvascular integrity

17. Restoring Normovolemia Hypervolemia

18. Maintaining Normovolemia No fluid shifts to interstitium GDT: priority conflict ?

19. Courtesy Mc Graw-Hill Companies Hypertonic #1. Spectacular (un-titrated) results

20. SolutionSodiummosm/L mmHg NS154 308 5944 LR130 275 5307 Mannitol(20%) -1100 21230 Mannitol(25%) -1375 26537 3% Saline5131026 19802 7.5% Saline12832400 46320 23.4% Saline40048008 154554 Osmotic Power NB: COP Plasma: 25mmHg Voluven: 36mmHg

21. Paradigm: moving endogenous water #2. Consider start & end-points ISS IVSICS

22. Dose: 4 ml/kg or 250 cc as initial bolus over 5-10 min Mechanism of action :.shifts water 1 st out of RBCs & endothelium into plasma, & then out of interstitium & tissue cells;.a rapid but transient improvement in intravascular volume & hemodynamics;.endothelial cell shrinkage decreases capillary hydraulic pressure  improves perfusion; Acute resetting (oversized) fluid spaces

23. 1.pre-hospital: pre-emptive shrinking ISS & ICS (penetrating) trauma 2.High ICP in hypotensive pts 3.Last “chance” in moribund pts with severe shock ? #3. Restrictive use ?

24. % vol expansion hours #3. Glycocalix ?

25. Tølløfsrud S et al. Anesth Analg 2001;93:823-831 euvolemia

26. #4. Adding a charged colloid ? 1)Reducing chloride load; 2)Intravascular retention;

27. CMS and CM-HES have a significantly longer intravascular persistence compared to HES.

28. The doctor fights for his theory, The patient for his life … Oscar Wilde