Fluids Watch the type and measure the quantity

Transcription

1 Critical Care Medicine Apollo Hospitals Fluids Watch the type and measure the quantity Ramesh Venkataraman, AB (Int. Med), AB (CCM) Senior Consultant, Critical Care Medicine Apollo Hospitals Chennai

2 My Talk Effect of Fluid therapy Quantitative toxicity Qualitative toxicity

3 Fluid Therapy - Rationale Hypovolemia common in critically ill Fluid administration Reverses shock Restores/sustains perfusion and oxygen delivery Renal benefits Encourages diuresis Contrast and Rhabdomyolysis Dilutes nephrotoxins

4 Does Fluid Therapy Benefit Critically Ill? Hypoperfusion theory alone too simplistic Organ injury from complex interaction of host and disease Excludes inflammatory and microcirculatory alterations Response to fluid therapy unpredictable Critical illness, pre-existing disease and pharmacotherapy Extent and duration of responsiveness unclear Capillary leak Fluids do not correct vasodilatation Prowle, J. R. et al. Nat. Rev. Nephrol. 10, (2014)

5 New EGDT trials ProCESS ARISE ProMISE NO MORTALITY BENEFIT!!! Huang D et al. Intensive Care Med ;Aug 20

6 Neutral balance vs +7 L positive 1/3 rd in shock

7 1. Fluid balance (per L/day) on 60-day mortality OR 1.61 (95% CI, , p<0.001) 2. Furosemide (per 100mg/d) on 60-d mortality OR 0.48 (95% CI, , p=0.007)

8 Murphy CV et al. CHEST 2009; 136:

9 RRT need lower in restrictive strategy group 10% vs 14% (P = 0.06)

10 Can fluid therapy hurt the kidney? Prowle, J. R. et al. Nat. Rev. Nephrol. 10, (2014)

11 Fluid balance in AKI Fluid overload independently associated with poor outcomes Early positive fluid balance predicts AKI after cardiac surgery Fluid overload at RRT initiation associated with increased death and impaired renal recovery Negative balance with RRT associated with increased RRT-free days Prowle, J. R. et al. Nat. Rev. Nephrol. 6, (2010) Schrier RW Clin J Am Soc Nephrol 5: , 2010

12 Under estimation of serum creatinine Delay in diagnosis of AKI Wrong categorization of AKI class

13 Fluid Overload and Organ Dysfunction

14 Fluid Overload and Mortality SOAP study (N=3147 patients) Multicenter observational study (24 European centers) 36% had Sepsis Positive fluid balance (72 hours) predicts mortality Odds ratio (per liter increase) = 1.1 ( ); p = Odds ratio (per liter increase) = 1.21 ( ); p = AKI patients more fluid overloaded than non-aki

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16 Fluid Overload and Mortality Observational study (N=618) > 10% increase in bodyweight from baseline PICARD study group Mortality Fluid overload at peak serum creatinine Less renal recovery (35 vs. 52%; P = 0.007) days 60 days Hospital DC Fluid Overload No Overload

17 Fluid Dose and Mortality

18 Beyond Starling Hydrostatic pressure Vs. Oncotic pressure Leaky capillaries interstitial edema Manipulation of colloid osmotic pressure ineffective Decreased rate of vascular refilling Potentiation of inflammation Myburgh JA et al. NEJM : 2013 : 369 ;

19 Natrituretic Peptides Shed Endothelial Glycolcalyx Jacob et al. Basic Res Cardiol (2013) 108:347

20 Beyond Starling Model Impaired glycocalyx Disruption of ECM Lymphatic dysfunction Prowle, J. R. et al. Crit. Care Clinics 2015 ( Article in press)

21 Fluids QuantitativeToxicity Dry and Fry Fill and kill Nephrologists Intensivists

22 Fluid Balance Paradigm Guided fluid resuscitation Even fluid balance Appropriate fluid removal McDermid RC et al. WJCCM 2014; 3(1): 24-33

23 Fluid Measure the Quantity Take Home Optimization of central hemodynamics critical in shock, but. Response to fluids magnitude and duration unpredictable Fluid overload consistently shown to increase AKI and mortality Emerging pathophysiological insights Desire to achieve adequate resuscitation has to be mitigated against the harmful effects of fluid overload Careful volume assessment to avoid hypovolemia and fluid overload imperative throughout critical illness

24 AKI Mortality Quantitative Fluid Toxicity But what fluid to give when needed? Does it matter? Hypovolemia Hypervolemia Euvolemia Fluid Quantity

25 Colloid or Crystalloid? Survival Time Organ dysfunction N = 6933 Duration of MV 4% albumin vs. 0.9% Saline Duration of RRT Albumin: Saline Volume = 1:1.4 NEJM 2004;350: ICU LOS Hospital LOS

26 N = 2857 Colloid HES, Gelatin, Dextrans, 5% or 20% albumin Crystalloid Isotonic/hypertonic saline/buffered solution

27 Are All Colloids The Same? Molecular weight and Number average molecular weight Monodisperse vs polydisperse Mw-Viscosity; Mn Oncotic pressure Osmolality Oncotic pressure Plasma half life Plasma volume expansion Acid-base composition Electrolytes

28 Hydroxyethyl Starch Solutions 1. Concentration High or Low 2. Avg Mol Weight Low, medium or high 3. Molar substitution - Low or high 4. C2/C6 ratio

29 Volume Expansion (%) Are All Colloids The Same? Hyperoncotic Colloids

30 (N=1013)

31 What about Starches? N = % Pentastarch (HES 200/0.5) vs. modified RL RL/HES ratio % vs. 22.8% ; P =0.02 Dose of HES independent predictor of both need of RRT and 90 day mortality

32 6S trial- NEJM July 2012 Higher rate of RRT at 90days N = 804 HES 6%/130/0.42 Upto 33ml/kg IBW

33 N = 7000 patients HES 6%/130/0.4-1:1.3 fluid ratio - No short-term hemodynamic benefits NEJM Nov 2012

34 Renal Events

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36 Colloids Summary Take Home Colloids do not reduce fluid requirement significantly Glycocalyx disruption 5% albumin to be avoided in TBI Hyperoncotic colloids should be avoided HES increases risks of AKI, RRT and mortality Results confounded by fluid overload Should we then use a crystalloid? If so which one?

37 Are all crystalloids the same? Dilutional Acidosis Why doesn t it happen with other bicarbonate poor fluids? Plasma volume expansion Dilution of bicarbonate Renal bicarbonate wasting Grotthus mechanism Excess proton generation Hyperchloremia a mere association!!

38 Determinants of [H + ] Blood Plasma OH - H + H 2 O Saline induced acidosis is secondary to pco 2 decreased SID caused by excess chloride Aload TOT - Decreased SID: Increased water dissociation and acidosis SID Stewart P. Can J Physiol Pharm 1983;61:1444

39 Saline Induced Acidosis Does it exist clinically? 1. Saline increases Cl- and decreases BE in a dose dependent manner 2. Saline cause moderate acidosis lasting 1-2 days 3. Respiratory compensation attenuates acidosis in an open system 4. Could be significant in patients with another acidemia 1 - Scheingraber S et al Anesthesiol 1999, 90: Boldt J et al. Anesth Analg 2009, 109: O Dell E et al. Crit Care Med 2007, 35:

40 Chloride And The Kidney 1. Hyperchloremia produces 1. Progressive renal vasoconstriction Tubuloglomerular Feedback 2. Fall in GFR that is independent of the renal nerves 3. Changes related to tubular Cl - reabsorption Chloride-induced vasoconstriction appears specific for the renal vessels Wilcox CS. J Clin Invest. 1983;71(3):

41 Does this acidosis pose problems? Renal Renal vasoconstriction and decrease in GFR Delayed time to micturition Decreased urine output and sodium excretion GI function Decreased gastric perfusion Prolonged gastric emptying time and ileus Postoperative nausea and vomiting Pro-inflammatory Cogulation abnormalities May trigger inappropriate therapies Guidet B et al. et al. Critical Care 2010, 14:325

42 Can we prevent Saline-induced acidosis? Large volume of NS Decrease in SID Decrease in A TOT Metabolic Acidemia Metabolic Alkalemia Therefore to prevent Saline induced acidosis, extracellular SID must fall during the infusion ONLY enough to counteract the progressive A TOT dilutional alkalosis (IDEAL SID = 24) 1 1-Morgan T et al. Crit Care Resusc 2003, 5:

43 What is a balanced fluid? The ideal balanced crystalloid is normotonic with a SID of 24 meq/l Achieved by excising chloride from NS and substituting bicarbonate Bicarbonate cannot be included in IVF Instability and precipitation Addition of other anions Acetate, Lactate, or Gluconate

44 What options do we have? Have no conflicts to declare Don t favour any particular product

45 Clinical Data Saline Prospective prescription open decreased label sequential (3.2 vs period 0.06 L/patient; study P.001) and 4% Done gelatin during solution entire from ICU (0.7 stay vs 0 L/patient; P.001) 5.05 Intervention L per patient period during NS, control 4% albumin period and % gelatin L per patient avoided during intervention Hartman s, period Plasmalyte- 148 and 20% albumin used Yunos Net al et al. JAMA, October 17, 2012 Vol 308, No. 15

46 Chloride rich fluid More AKI and RRT AKI (OR [95% (CI, ); P = 0.001] Reduction in the increase of mean creatinine level from baseline to peak ICU level Use of RRT (OR [95% CI, ]; P=0.004)

47 Annals of Surgery Volume 255, Number 5, May 2012 Retrospective cohort study using a large, US automated hospital claims database Exclusively 0.9% saline or Plasma-Lyte A or Plasma-Lyte 148 on the day of surgery 3:1 propensity match 926:2778 patients analysed

48 Annals of Surgery Volume 255, Number 5, May 2012

49 N = % balanced crystalloid

50 AKI Mortality Fluid Toxicity Watch the type Fluid type Hypovolemia Hypervolemia Euvolemia Fluid Quantity

51 Fluids Watch the Type and measure the Quantity Take Home Volume and choice of fluid seem to impact renal function and mortality Context of fluid therapy profoundly alters risk/benefit Early aggressive resuscitation of shock followed by a conservative strategy seems prudent Choose your poison carefully Avoid hyperoncotic albumin and HES Avoid hyperchloremia

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53 HCl loading in a normal 70kg man 10 mmol/l 1N HCl SID [H+] ph HCO pco 2 = 40 ATOT = 15 Na + = 143 Cl - = 110

54 Physico-chemical Approach Both H + and HCO3 - are dependent variables Bicarbonate just a gap filler between strong cations and anions Metabolic component Strong Ion Difference and Atot Respiratory component PCO2 Six acid-base disorders SIDe increase and decrease alkalosis and acidosis A TOT increase and decrease acidosis and alkalosis Respiratory

55 mmol/l Acid Load 3hrs Post-endotoxin Mean acid load 8.7 mmol/l CO2 (3.1%) Lactate (9.6%) SIG (7.7%) Saline (37.4%) Unknown (42.2%) dog # Kellum et al. Shock 1998; 9:

56 SID vs ph & [H + ] ph [H+] nmol/l [SID] meq/l

57 Regional Blood Flow Variation

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59 Fluid balance in AKI Fluid overload independently associated with poor outcomes Early positive fluid balance predicts AKI after cardiac surgery Fluid overload at the commencement of RRT associated with increased death and impaired renal recovery Negative balance with RRT associated with increased RRT-free days

60 Fluid overload - Marker or Mediator? SOAP study definition of AKI Stage 3 only ARDS FACT study Adverse effects of fluid in early AKI group?dilution of serum creatinine Increased fluid overload at dialysis initiation?paradigm shift EGDT study Equal volume at 72 hours (13-14L) Fluid overload Cause vs. effect Direct Indirect marker of severity Intolerance to fluid removal Harm from fluid removal Harm from ineffective fluid removal

61 Natrituretic Peptides Shed Endothelial Glycolcalyx Jacob et al. Basic Res Cardiol (2013) 108:347

62 Fluid Resuscitation Fluid resuscitation is the most frequent intervention in the ICU Normal saline is the commonest fluid used for resuscitation Standard against which other solutions are measured/compared Resuscitation with normal saline causes metabolic acidosis Cardiopulmonary bypass Handy JM et al. British Journal of Anaesthesia 101 (2): (2008) Hayhoe et al. Intensive Care Med. 25: ; 1999

63 Physico - chemical approach H + and HCO3 are only DEPENDENT variables Determinant of H+ is water dissociation Aqueous Solutions Water Dissociation Acids increase water dissociation H 2 O H + + OH -

64 Strong Ion Difference (SID) Mg ++ Ca ++ K + Na + Cl - Others (lactate, etc) These are the Strong Ions, so-called because they do not readily combine with other ions or lose their charge. Conversely, H + and HCO 3 - readily combine, and are called weak ions Normal extracellular fluid SID is 40 Decrease in SID increases water dissociation

65 Stewart Approach

66 Its not the chloride silly!!!! It s the SID of the fluid that matters!!! Story DA et al. Anesth Analg 2006;103:144 8

67 Is all acidosis the same? Gunnerson K et al. et al. Crit Care 2006, 10:R22