The Crystalloid vs. Colloid Controversy Continues Karl E. Jandrey, DVM, MAS, DAVCECC Associate Professor of Clinical Small Animal Emergency & Critical Care 2 nd Annual Conti Symposium, UC Irvine August 3, 2014 Current Concepts and Controversies in Small Animal Critical Care Goals and Objec.ves Fluid Physiology and Behavior Review & New Understandings Crystalloids & Colloids in the ICU Evidence from human studies Decision- making The Challenge J v /A = L p { (P c - P i ) σ (π p - π i ) } J v = Volume filtra.on rate A = Endothelial area L p = Coefficient of fitra.on P = Hydrosta.c pressure π = Osmo.c pressure σ = Osmo.c reflec.on coefficient 1
J v /A = L p { (P c - P i ) σ (π p - π i ) } J v = Volume filtra.on rate A = Endothelial area Difference Extravascular fluid between L p flux: = Coefficient fluid capillary of fitra.on blood movement across pressure and P semipermeable = Hydrosta.c Inters..al membranes hydrosta.c π = Osmo.c pressure σ = Osmo.c reflec.on coefficient Difference between plasma and inters..al osmo.c pressure J v /A = L p { (P c - P i ) σ (π p - π i ) } Pi σ π i π p J v /A Starling Principle: Classic Model Levick and Michel, Cardio Res 2010,87:198-210. 2
7/13/14 Starling Principle: Revised Model Glycocalyx Model Levick and Michel, Cardio Res 2010,87:198-210. Myburgh & Mythen, NEJM 2013,369(13):1243-1251. 3
Capillaries are not Created Equally Woodcock, Br J Anesth 2012,108(3):384-394. J v /A σ Inters..al Intracellular Intravascular J v /A σ Plasma Inters..al Intracellular 4
Original Starling Principle IV volume = plasma and cells Capillaries separate plasma [high protein] from inters..al [low protein] spaces Revised Starling + Glycocalyx Model IV volume = glycocalyx + plasma + RBCs Inters..al and plasma volumes communicate directly where there are discon.nuous capillaries. Open fenestrated capillaries produce glomerular filtrate. EGL is semipermeable to anionic proteins and their concentra.on in the cled is low. Con.nuous capillaries exhibit no absorp.on Important force is between transendothelial pressure and plasma- inters..al COP difference. Fluid is filtered from the arterial end of the capillary and reabsorbed at the venous end. Lymph return is small. Important force is transendothelial pressuredifference and plasma- subglycocalyx COP difference. Jv is much less than predicted and the major route for return of fluid to the circula.on is as lymph. Original Starling Principle Raising plasma COP enhances absorp.on and shids fluid from inters..um to plasma. At subnormal capillary pressure, net absorp.on increases plasma volume. At supranormal capillary pressure, net filtra.on increases inters..al volume. Infused colloid solu.on is distributed through the plasma volume, and infused isotonic salt solu.ons through the extracellular volume. Revised Starling + Glycocalyx Model Raising plasma COP reduces Jv but does not cause reabsorp.on. At subnormal capillary pressure, Jv approaches zero. Autotransfusion is acute, transient, and limited ~(500ml in humans). At supranormal capillary pressure, when the COP difference in maximal, Jv is propor.onal to transendothelial pressure difference. Infused colloid solu.on is ini#ally distributed through the plasma volume and infused isotonic salt solu.ons through the intravascular volume. At supranormal capillary pressure, infused colloid solu.on preserves COP, raises capillary pressure, and increases Jv. At supranormal capillary pressure, infused isotonic salt solu.on also raises capillary pressure, but it lowers COP and thus increases Jv (more than the same volume of colloid). Adapted from Woodcock, BJA 2012,108(3):384-394. What do we know now Classic Starling Revised Starling and Glycocalyx model How this new concept helps us to understand fluid therapy and the pa.ent response 5
Colloids vs. Crystalloid Recent Randomized Human Trails SAFE study Albumin vs. 0.9% NaCl CHEST study HES in 0.9% NaCl vs. 0.9% NaCl 6S HES in Ringer s acetate vs. Ringer s acetate CRISTAL Crystalloids vs. colloids in hypovolemic shock The Saline vs. Albumin Fluid Evalua.on Study Finfer et al,nejm 2004,350(22):2247-2256. The Saline vs. Albumin Fluid Evalua.on Study Blinded, randomized controlled trial 6997 adults in 18 ICUs 4% albumin (3497) vs. 0.9% NaCl (3500) Outcome measure: death at 28 days Results: no difference in death rate development of new organ failure LOS, mechanical ven.la.on, RRT Finfer et al,nejm 2004,350(22):2247-2256. 6
The Saline vs. Albumin Fluid Evalua.on Study Finfer et al,nejm 2004,350(22):2247-2256. The Saline vs. Albumin Fluid Evalua.on Study Finfer et al,nejm 2004,350(22):2247-2256. Crystalloid vs. Hydroxyethyl Starch Trial Myburgh et al,nejm 2012,367(20):1901-1911. 7
Crystalloid vs. Hydroxyethyl Starch Trial Blinded, randomized controlled trial 7000 adults in 32 ICUs 6% HES (130/0.4) vs. 0.9% NaCl Outcome measure: death at 90 days Results: no difference in death rate (6 predefined subgroups) HES Tx à need for RRT Myburgh et al,nejm 2012,367(20):1901-1911. Crystalloid vs. Hydroxyethyl Starch Trial Myburgh et al,nejm 2012,367(20):1901-1911. Crystalloid vs. Hydroxyethyl Starch Trial Myburgh et al,nejm 2012,367(20):1901-1911. 8
Crystalloid vs. Hydroxyethyl Starch Trial Myburgh et al,nejm 2012,367(20):1901-1911. Crystalloid vs. Hydroxyethyl Starch Trial Myburgh et al,nejm 2012,367(20):1901-1911. Scandanavian Starch for Severe Sepsis/Sep.c Shock (6S) Trial Perner et al, NEJM 2012,367(2):124-134. 9
Scandanavian Starch for Severe Sepsis/Sep.c Shock (6S) Trial Blinded, randomized controlled trial 800 adults ICUs 6% HES (130/0.42) vs. Ringer s acetate Outcome measure: death at 90 days Results: 1.17 increase in rate of death with HES HES Tx à 35% rela.ve increase in RRT Similar to 10% HES (200/0.5) in another trial Perner et al, NEJM 2012,367(2):124-134. Scandanavian Starch for Severe Sepsis/Sep.c Shock (6S) Trial Perner et al, NEJM 2012,367(2):124-134. Scandanavian Starch for Severe Sepsis/Sep.c Shock (6S) Trial Perner et al, NEJM 2012,367(2):124-134. 10
CHEST and 6S No significant difference in short- term hemodynamic endpoints HES:crystalloid ~1:1.3 Similar to SAFE and other trials Cochrane Review 2013 Colloids vs. crystalloids for fluid resuscita.on in cri.cally ill pa.ents (Perel et al) There is no evidence from randomized controlled trials that resuscita.on with colloids reduces the risk of death, comparede to resuscita.on with crystalloids, in pa.ents with trauma, burns, or following surgery. Furthermore, the use of hydroxyethyl starch might increase mortality. Colloids vs. crystalloids for the Resuscita.on of the Cri.cally Ill (CRISTAL) Trial Annane et al, JAMA 2013,310(17):1809-1817. 11
CRISTAL Trial Open label, randomized controlled trial 2857 adults in 57 interna.onal ICUs Mul.ple colloids vs. mul.ple crystalloids Outcome measure: death at 28 days Results: No difference in 28 day mortality Colloids favored at 90 day mortality Annane et al, JAMA 2013,310(17):1809-1817. CRISTAL Trial Annane et al, JAMA 2013,310(17):1809-1817. CRISTAL Trial Annane et al, JAMA 2013,310(17):1809-1817. 12
What is it about 0.9% NaCl? Most commonly used crystalloid worldwide Strong ion difference is zero Results in hyperchloremic metabolic acidosis Worries about renal and immune func.ons Is a balanced crystalloid bezer? Is there a difference amongst crystalloids? Raghunathan et al,ccm 2014,42(7):1585-1591. 13
Is there a difference amongst crystalloids? Retrospec.ve cohort of sep.c pa.ents 360 US ICUs 53,448 adults Stra.fied based on fluids received Outcome measure: hospital mortality > day 2 Raghunathan et al,ccm 2014,42(7):1585-1591. Is there a difference amongst crystalloids? Raghunathan et al,ccm 2014,42(7):1585-1591. What does the future hold? A Comparison of High and Low Chloride Containing IV Fluid Solu.ons in Pa.ents Undergoing Major Surgery and/or ICU Admission Expected 3000 adults, Mortality at 7 days Secondary: LOS, renal failure, dysrhythmias, infec.on, electrolyte disorders. 14
And an experimental canine study Gauthier et al, JVECC 2014,24(3):251-258. Crystalloids vs. colloids, canine SIRS Randomized, placebo- controlled, blinded 16 Beagles, cross- over 40ml/kg 0.9% NaCl vs. tetrastarch (130/0.4) Gauthier et al, JVECC 2014,24(3):251-258. Crystalloids vs. colloids, canine SIRS Similar changes in hemodynamics and lab values in dogs with LPS- induced inflamma.on Tetrastarch produced larger increase in heart rate and blood pressure in first 2 hours No long term follow- up Renal parameters not measured Gauthier et al, JVECC 2014,24(3):251-258. 15
Future Direc.ons Use human studies to help understand our pa.ents fluid needs for cri.cal illness Remember that human studies use 0.9% NaCl far more oden than balanced solu.ons. Veterinary clinical prac.ce may not exactly reflect these tradi.ons/studies. There is no perfect fluid choice for all disease states. 16