Fluid Management in the Critically-Ill

Transcription

1 Fluid Management in the Critically-Ill Dan Schuller, M.D. Professor and Chair Department of Internal Medicine - Transmountain Texas Tech University Health Sciences Center El Paso Paul L. Foster School of Medicine. Disclosures / Conflict of Interest None Educational Objectives: Identify the key principles of optimal fluid resuscitation in the multidisciplinary ICU environment Improve patient care through collaborative, timely and individually tailored fluid replacement Recognize the impact that fluid management has on outcomes 1

2 FLUID MANAGEMENT Outline: Historical perspective Clinical reasoning in fluid management Physiology and Pathophysiology assumptions Determinants of oxygen delivery Frank-Starling curve Starling forces in the capillary Glycocalyx Fluid phases of shock Pharmacokinetics and pharmacodynamics of fluids Adverse consequences of fluid overload Resuscitation fluids: crystalloids, colloids, blood products Historical Perspective 1830: R. Hermann analyzed the blood of patient with cholera describing hemo-concentration 28% less fluidity and thinking that the thickening of the blood prevents its circulation Jachnichen injected 6 oz of water IV in a patient with cholera describing an improvement in pulse lasting 15 minutes but patient died 2 hours later. 1831: Indian Blue Cholera Pandemic reached England 1831: O Shaughessy (age 22) proposed treating cholera by the injection of highly oxygenated salts into the venous system (Lancet Dec 10 th, 1831) 1832: Lewins published in Lancet the effect of fluid resuscitation in three patient with cholera achieving the most wonderful and satisfactory effect and recommending repeated injections of large quantities of solutions guided by the patient s pulse and symptoms. Awad S, et al. The history of 0.9% saline. Clinical Nutrition (2008) 27,

3 Historical Perspective 1832: Robert Lewins described the effects of alkalinized IV fluids during cholera pandemic: the quantity necessary to be injected will probably be found to be dependent on the quantity of serum lost. 1885: Alexis Hartmann and Sidney Ringer developed modified solutions for rehydration of children with gastroenteritis 1896: Earnest Starling determinants of transvascular exchange 1941: Blood fractionation. Human albumin first used in large quantities for resuscitation of burned patient after the attack on Pearl Harbor. Historical Perspective 1942: Gelatin is discussed for resuscitation (War) Dextran is developed in Sweden Coconut water used in Vietnam First production of Hydroxyethyl Starch (HES) Several new HES Products are developed 3

4 Historical Perspective 2001: 2004: 2004: 2006: 2007: EGDT (Early Goal Directed Therapy) SAFE (Saline vs Albumin Fluid Evaluation) VISEP(Volume Subst and Insulin Therapy in Sepsis) FACTT (Fluid and Catheter Treatment Trial) Structure and function of the endothelial glycocalyx Historical Perspective 2011: 2012: 2012: 2013: : : 2014: FEAST (Fluid Expansion As Supportive Therapy) CHEST (Crystalloid vs Hydroxy Ethyl Starch Trial) CRYSTMAS ( 6% HES vs 0.9% NS in Severe Sepsis) CRISTAL (Colloid vs Crystalloid in Hypovol Shock) ProCESS, ARISE and ProMISE ALBIOS (Albumin Replacement in Severe Sepsis) TRISS (Transfusion Requirements in Severe Sepsis SEPSISPAM (High vs Low BP targets in Septic Shock) Historical Perspective 2015: : SPLIT (Buffered Crystalloid vs Saline and AKI) EARSS (Efficacy & Tolerance of Albumin in Septic Shock) SALT (Isotonic Solution Administration Logistical Testing) SALT-ED (Balanced Crystalloids vs Saline in Non-critically Ill) SMART (Balanced Crystalloids vs Saline in Critical Care Adults) Restrictive vs Liberal Fluid Therapy after Major Abdominal Surgery PAMPer (Prehospital Plasma during Air Medical Transport in Trauma) More to follow. 4

5 Chronic Controversies Regarding Fluid Management in Acute or Critically-ill Patients Early vs Late Crystalloids vs Colloids Saline vs Balanced Solutions Bundled vs Unbundled Protocol vs Personalized Bolus vs Continuous Dry vs Wet Clinical Reasoning Diagnostic Integration of clinical information, medical knowledge and situational factors for diagnosis Poor diagnostic reasoning contributes to medical errors and contributes to 10% of patients deaths and adverse events Means to an end Primarily a classification task (assigns labels to constellation of symptoms). These labels shape the understanding of the illness and facilitate communication. Management Choices about treatments, f/u visits, referrals, allocation of resources, etc. Priority: we frequently have to manage before a secure diagnosis Usually considering multiple options, side effects Cook D.A, et al. JAMA. May 10 th, 2018 Clinical Reasoning Diagnostic Means to an end Correct vs incorrect Not influenced by values and preferences Can be done in isolation of the patient Finite range of conclusions and interacting factors Uncertainties can be accommodated with less specific labels Cook D.A, et al. JAMA. May 10 th, 2018 Management Usually a process and an end Multiple options. It depends on risks, side effects, social values, logistical constrains, cost, resource availability Requires communication and shared decision making with patient, relatives, health care providers, insurance agencies Inherently fluid, dynamic, requiring monitoring and frequent adjustments More complex, with uncertainties, less predictable responses, more contingencies 5

6 Management reasoning flaws regarding fluids in ICU Universally used but with significant knowledge gaps None of the IV fluids currently available were formally evaluated for safety and efficacy Providers don t take fluids seriously IV Fluids = Prescription Drug Indications, contraindications, dosing, therapeutic range, toxicity, risks and benefits. Providers forget that fluid resuscitation is a process but also an end Frequently ignoring cost and resource availability Never a shared decision in the ICU Multiple variable skills inconsistently used are required to assess response to treatment and follow-up Questions regarding fluid management Is fluid indicated? Which fluid? When do I give it? What amount? For how long? How do I give it? How do I monitor response? How do I monitor side effects or toxicity? How do I remove it? Determinants of Oxygen delivery (DO2) CaO2= (Hgb x 1.34) O 2 Sat + PaO2 (0.003) DO2 = CO X CaO2 Preload Contractility Afterload 6

7 Fluid Management: Frank - Starling Curve Concern: Increase in capillary hydrostatic pressure (particularly in patients with lung injury) oxygenation Extravascular lung water (EVLW) Worse prognosis Determinants of Oxygen delivery (DO2) CaO2= (Hgb x 1.34) O 2 Sat + PaO2 (0.003) DO2 = CO X CaO2 Preload Contractility Afterload Conservative fluid management Diuresis Over diuresis Fluid removal (CRRT, ihd) 7

8 Starling Forces in the Capillary J v =L p [(P c -P if )-σ(π c - π if )] Jv = Volume flow of fluid Lp = Hydraulic Conductivity P=Hydrostatic pressure in capillary (P c ) or interstitial fluid (P if ) σ = Reflection Coefficient (0 1) π = Colloid Osmotic Pressure in Plasma (π c ) or interstitial fluid (π if ) Starling Forces in the Capillary 8

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10 Woodcock T.E, Woodcock T.M, British Journal of Anesthesia 108(3): (2012) Colbert JF, Schmidt EP. Clin Chest Med 2016 ;37(2): Role of the Endothelial Glycocalyx Layer in the Use of Resuscitation Fluids. Myburgh J.A, Mythen M.G. N Eng J Med 2013; 369:

11 Ideal Fluid Management Rational Considers indications, contraindications and side effects Individualized, tailored to the clinical situation Fluid stewardship Four D s: Drug, Dose, Duration, De-escalation Evidence based Multiple large multicenter RCT s Cost effective Personalized fluid management: CIT TAIT Context Indication Targets Timing Amount of fluid Infusion strategy Type of fluid van Haren. Critical Care 2017; 21 (Suppl 3):45-73 Fluid, fluid phases during shock: Resuscitation, Optimization, Stabilization and Evacuation Malbrain ML, et al. Ann Intensive Care 2018;8:66 11

12 Pharmacokinetics and pharmacodynamics of fluids Hahn RG et al: Anesthesiology 2010;113(2): Hahn RG et al: Eur J Anesthesiol 2016;33(7): Pharmacokinetics and pharmacodynamics of fluids Hahn RG et al: Anesthesiology 2010;113(2): Hahn RG et al: Eur J Anesthesiol 2016;33(7): Pharmacokinetics and pharmacodynamics of fluids Solid line: 500 ml HES Dashed line: 1 L Ringer s Hahn RG et al: Anesthesiology 2010;113(2): Hahn RG et al: Eur J Anesthesiol 2016;33(7):

13 Five Indications for Intravenous Fluids: Resuscitation Maintenance of total body water and electrolytes Replacement of total body water and electrolytes Carriers for intravenous medications Parenteral nutrition Potential consequences of fluid overload on end-organ function From: Malbrain ML, et al. Ann Intensive Care (2018) 8:66 Ideal Resuscitation I.V. fluid Widely available Predictable and sustained increase in intravascular volume Composition similar to extracellular fluid Metabolized and completely excreted without accumulation Safe, no side effects Use supported by evidence, multiple large RCT s Cost effective 13

14 Currently available ideal fluid Types and Compositions of Resuscitation Fluids. Myburgh JA, Mythen MG. N Engl J Med 2013;369: Which Resuscitation Fluid? Colloids Human albumin (4%, 5%, 20-25%) Semisynthetic colloids Hydroxyethyl starch solutions (HES) (Hemohes, Hextend, Volulyte,Venofundin,Tetraspan) Gelatins (Gelofusine, Haemaccel) Dextrans Crystalloids 0.9 % NS Balanced solutions (Hartmann s, Ringer s or Plasmalyte) Combinations: D5NS, D5/0.45%, D5LR, etc Blood products 14

15 Albumin for Resuscitation Albumin in patients with hypovolemia, burns or hypoalbuminemia was associated with a 6% absolute increase risk of death (RR 1.68; 95% [CI], ; p<0.01) (Cochrane Injuries Group Albumin Reviewers. BMJ 1998;317:235-40) Saline vs Albumin Fluid Evaluation (SAFE) showed no significant difference in mortality or development of organ failure(rr 0.99; 95% [CI], ; p= 0.87). (N Eng J Med 2004;350: ) Albumin associated with increase risk of death in TBI (RR 1.63; 95% [CI], ; p=0.003). (N Eng J Med 2007;357:874-84) Resuscitation with albumin in severe sepsis associated with decrease risk of death at 28 days (RR 0.71; 95 % [CI] ; p = 0.03) (Finfer S, et al Intensive Care Med 2011;37:86-96) Albumin replacement in addition to crystalloids in severe sepsis-albios (n=1,818) did not improve the 28 or 90 day survival in-hospital mortality. However, post hoc subgroup analysis of patients in shock showed fewer deaths in albumin group (RR 0.87; 95 5 [CI] ; p=0.03) (Caironi P et al.n Eng J Med 2014;370: Albumin for Resuscitation SAFE; Overall mortality (n=6,997) ALBIOS (n=1,810) SAFE; TBI subgroup (n=460) N Eng J Med 2004;350: N Eng J Med 2014; 370: N Eng J Med 2007;357: Meta-Analysis of Mortality in Large-Scale Randomized Trials Severe Sepsis. Comparing Albumin with Crystalloids in Adult Patients with Severe Sepsis Wiedermann C.J. Joannidis M. N Engl J Med 2014;371:

16 Semisynthetic Colloids for Resuscitation Gelatins Dextrans Hydroxyethyl starch amylopectin Adverse events: Increased risk of AKI: Allergic reactions: Bleeding: prepared by hydrolysis of bovine collagen biosynthesized from sucrose by bacteria from maize derived D-glucose polymer HES and gelatin Gelatins and dextrans Dextrans and HES Semisynthetic Colloids for Resuscitation VISEP trial: 2X2 factorial trial. Intensive insulin therapy vs conventional and LR vs. 10% HES 200/0.5 ( n=537) in severe sepsis. Stopped early for increase AKI (34.9% vs 22.8 %, p=0.002) and trend toward increase 90 day mortality 41% vs 34%, p =0.09).(Brunkhorst FM, et al. NEJM 2008;358: ) CRYSTMAS trial: 6% HES 130/0.4 vs 0.9% NS (n=196) severe sepsis. Mortality 31% vs 25% and AKI 24.5 vs 20%, NS. (Guidet B, et al. Critical Care Lond Engl. 2012;16:R94) Scandinavian critical care trials group: 6% HES 130/0.42 vs Ringer s acetate (n=804); Renal replacement therapy (22% vs 16%, p=0.04) and 90 day mortality (51% vs 43%, p=0.03) higher with HES (Perner A,et al. NEJM 2012; 367: ) Hydroxyethyl Starch 130/0.42 versus Ringer's Acetate in Severe Sepsis Perner A et al. N Engl J Med 2012;367:

17 Semisynthetic Colloids for Resuscitation CRISTAL trial: ( n=2,857) ICU patients, 55% with sepsis compared colloid (HES and gelatin) vs crystalloid (LR and 0.9% NS). Similar 28 day mortality (25% vs 27%, p=0.26), but improved 90 day mortality (30.7% vs 34.2, p=0.03) in favor of colloids (Annane D, et al. JAMA. 2013;310: ) CHEST trial: (n=7,000, 1,937 with sepsis) 6% HES 130/0.4 vs 0.9% NS.HES associated with more AKI, renal replacement therapy (7.0% vs 5.8%, p=0.04) and similar 90 day mortality (18% vs 17%).(Myburgh JA, et al. N Eng J Med 2012;367;20: ) Meta-analysis showed association of HES with increased mortality and AKI. (Zarychanski R, et al. JAMA 2013;309: ) Hydroxyethyl Starch or Saline for Fluid Resuscitation in Intensive Care Myburgh JA, et al. N Eng J Med 2012; 367 (20) Crystalloids for Resuscitation: Which one? 0.9% sodium chloride is ABnormal saline 0.9% NS = ph 5.6; Na+ 154, Cl- 154, osmolality 308 Large volume 0.9% NS can result in hyperchloremic metabolic acidosis Hyperchloremic solutions cause renal vasoconstriction, decrease GFR Emerging concerns regarding affecting glycocalyx integrity More than 40 million bags of saline are produced every month Recent critical shortages of saline solutions due to manufacturing and supply process. 17

18 8/14/2018 Crystalloids for Resuscitation: Which one? In a randomized, controlled, double-blind, cross-over study comparing 2 L infusion of 0.9% NS vs PlasmaLyte in health volunteers, 0.9% saline resulted in decrease renal blood flow velocity and cortical tissue perfusion (Chowdhury AH, et al. Ann Surg 2012;256 (1):18-24) In a prospective, open-label, sequential pilot study (n=1,533) ICU patients, implementation of a chloride restrictive strategy resulted in a significant decrease in incidence of AKI and the use of RRT (Yunos NM, et al. JAMA 2012; 308 (15): ) 18

19 Crystalloids for Resuscitation: Which one? In a double-blind, cluster, randomized, double cross-over trial comparing a buffered crystalloid vs saline there was no difference in the risk of AKI (Young P, et al. JAMA 2015;314 (16): ) Crystalloids for Resuscitation: Which one? SMART Pragmatic, cluster-randomized, multiple cross-over trial in 5 ICU s at Vanderbilt (n=15,802) compared 0.9% saline vs balanced crystalloid. 0.9% NS resulted in higher rate of composite outcome of death, renal replacement therapy or persistent renal dysfunction 19

20 Crystalloids for Resuscitation: Which one? SALT-ED compared saline vs. balanced crystalloids in the ED and subsequent hospitalization in non-critical patients outside of ICU. (n=13,347), single center, unblinded, pragmatic design, multiple crossover trial. No difference in primary endpoint of hospital free days to day 28. However, lower incidence of composite of death, new RRT and persistent renal dysfunction. Blood Products for Resuscitation Restrictive transfusion strategy for ICU, medical and most surgical patients. Threshold for PRBC transfusion typically Hgb < 7.0 In trauma patients, the goals, targets and strategy for resuscitation is variable depending on context: Blunt injury SBP mmhg Penetrating injury SBP mmhg +/- TBI SBP (MAP > 70 ) For massive transfusion, trend toward whole blood if available or component therapy (FFP: platelets: PRBC) with a 1:1:1 or 1:1:2 Watch for complications: TRALI, TACO, TRIM Hgb based blood substitutes (Hgb based oxygen carriers :HBOC s ; Hemopure,Hemospan) have encountered barriers in production and development due to ADR s (AKI, stroke and vasoconstriction) Holst et al. N Eng J Med 2014; 371: Wise R, et al. World J Surg 2017; 41:

21 Prehospital administration of FFP associated with improved survival in trauma patients. Sperry J.L et al. PAMPer Study Group. N Eng J Med 2018; 379: Conclusions and Recommendations regarding Fluid Management in the Critically-ill Fluid management should be fluid and administered with the same precautions used with any intravenous drug stewardship. Consider indication, timing, type, dose, contraindication, toxicity, deescalation & cost. No overall benefit of albumin over crystalloids except in small subset of medical patients. Strong evidence against use of albumin in TBI Strong evidence against using semi-synthetic colloids for resuscitation Mounting evidence supporting balanced crystalloids over 0.9% saline Consider possible role for early FFP in trauma patients at risk for shock. 21

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