FLUID BALANCE AND ACUTE KIDNEY INJURY. Ravindra L. Mehta MD. DM, FACP, FRCP University of California San Diego

Transcription

1 FLUID BALANCE AND ACUTE KIDNEY INJURY Ravindra L. Mehta MD. DM, FACP, FRCP University of California San Diego SLANH and Chilean Society of Nephrology Coquimbo, Chile Sep 29, 2010

2 Fluid Balance and Acute Kidney Injury Topics What s known in 2010? Practical Implications Future Directions

3 Fluid Balance and Acute Kidney Injury Topics What s known in 2010? n Fluid Accumulation is associated with adverse outcomes

4 Summary of clinical studies showing an association between fluid balance and clinical outcome

5 Alsous et al: Negative Fluid Balance Predicts Survival in Patients With Septic Shock* CHEST 2000; 117: ) Design: Single Center retrospective analysis of ICU patients Patients: 36 pts with septic shock Comparisons: Variables were compared between survivors and nonsurvivors and in patients who did vs those who did not achieve negative (< 500 ml) fluid balance in > 1 day of the first 3 days of management. Outcomes: Hopsital mortality Survival risk ratios (RRs) were used as the measure of association between negative fluid balance and survival. RRs were adjusted for age, APACHE II scores, SOFA scores on the first and third days, and the need for mechanical ventilation, by stratified analyses.

6 Alsous et al: Negative Fluid Balance Predicts Survival in Patients With Septic Shock* CHEST 2000; 117: ) RRs for Survival in Patients With Septic Shock Who Achieved at > 500 ml Negative Fluid Balance on 1 of the First 3 Days of Treatment Compared to Those Who Did Not, Stratified for Other Known Predictive Variables*

7 Foland J et al Fluid overload before continuous hemofiltration and survival in critically ill children: a retrospective analysis. Crit Care Med Aug; 32(8): %FO was defined as total fluid input minus output (up to 7 days before CVVH for both hospital stay and ICU stay) divided by body weight.

8 Pediatric Patients: Higher percentages of fluid overload (FO) at dialysis initiation linked with increased mortality Goldstein, Pediatrics 2001 %FO was defined as total fluid input minus output (up to 7 days before CVVH for both hospital stay and ICU stay) divided by body weight. Foland, Crit Care Med 2004 Gillespie, Pediatr Nephrol 2004 Goldstein, KI 2005 Foland J et al. Crit Care Med Aug;32(8):

9 Pediatric Patients: Higher percentages of fluid overload (FO) at dialysis initiation linked with increased mortality Setting & Participants: 297 children from 13 centers across the United States participating in the Prospective Pediatric CRRT Registry. %FO was defined as a percentage equal to (fluid in [L] fluid out [L])/(ICU admit weight [kg]) 100%. Predictor: Fluid overload from intensive care unit (ICU) admission to CRRT initiation, Outcome & Measurements: The primary outcome was survival to pediatric ICU discharge. Results: The association between degree of fluid overload and mortality remained after adjusting for intergroup differences and severity of illness. The adjusted mortality OR was 1.03 (95% CI, ), suggesting a 3% increase in mortality for each 1% increase in severity of fluid overload. When fluid overload was dichotomized to 20% and 20%, patients with 20% fluid overload had an adjusted mortality OR of 8.5 (95% CI, ). N=153 N= 51 N= 93 Sutherland et al: AJKD 2010, 55: 316

10 In septic patients with AKI, fluid overload was associated with decreased survival at 60 days Payen et al. Critical Care 2008, 12:R74

11 In septic patients with AKI, fluid overload was associated with decreased survival at 60 days Of the 1,120 patients with ARF, 842 (75%) had early-onset ARF (occurring within 2 days of ICU admission) and 278 (25%) had lateonset ARF (occurring more than 2 days after ICU admission). Kaplan-Meier survival curves Payen et al. Critical Care 2008, 12:R74

12 1. Fluid Accumulation is associated with adverse outcomes Effect of Fluid Overload in Critically Ill Patients with AKI PICARD Study (618 critically ill patients with AKI, 396 required dialysis Dialyzed Patients Non- Dialyzed Patients Adjusted OR for death with %FO >10% at dialysis initiation: 2.07 (95% CI ) Adjusted OR for death with %FO >10% at dialysis cessation: 2.52 (95% CI )

13 Duration of Fluid Overload

14 Effect of Correction of Fluid Overload Effect of fluid overload correction on survival when %FO >10% at dialysis initiation : %FO 10% at dialysis end %FO > 10% at dialysis end Survival rate 65% 44% Mean % FO at dialysis cessation Survivors Nonsurvivors 13.0% 22.1% Adjusted OR for death with %FO >10% at dialysis cessation: 2.52 (95% CI ) PICARD Data Bouchard et al 2009 p P

15 Influence of Modality on Fluid Overload Mean percentage fluid overload Days

16 Vieira et al: Effect of acute kidney injury on weaning from mechanical ventilation in critically ill patients* Crit Care Med 2007; 35: ) Design: Single Center retrospective analysis of ICU patients in a cancer hospital Patients: 140 patients 93 with AKI and 47 controls requiring mechanical ventilation > 48 hrs. AKI defined as at least one measurement of serum creatinine >1.5 mg/dl during the ICU stay. Comparisons: Weaning parameters combination of positive end-expiratory pressure of <8 cm H2O, pressure support of <10 cm H2O, and FIO2 of <0.4, with spontaneous breathing. Outcomes: Duration of mechanical ventilation and duration of weaning

17 Fluid Balance and Acute Kidney Injury Topics What s known in 2010? n Fluid Accumulation is associated with adverse outcomes n Pathophysiology of Fluid shifts in critical illness

18 Fluid Balance and Acute Kidney Injury Pathophysiology of fluid shifts in critically ill patients

19 Third Space: Fact or Fiction? Intracellular fluid comprises twothirds of the body water. The remaining one-third about 15 l in the normal weighted adult comprises the extra-cellular volume (ECV, namely 20% of the total body mass) consisting of the plasma (about 3 l), the interstitial space (about 12 l) and small amounts of the so-called transcellular fluids such as GI secretions, CSF and ocular fluid. The latter are considered to be anatomically separated and not in dynamic equilibrium with the interstitial space and the plasma, in which water and small solutes can easily be exchanged. The third space, nothing more than a perception so far, has functionally been allocated to this trans-cellular compartment. Jacob et al: Best Practice & Research Clinical Anaesthesiology 23 (2009)

20 Response to Fluid Administration Distribution of infused fluids (dextrose (50 g/l), saline (9 g NaCl/l) and colloids) in the body water compartments. ECF, extracellular fluid; ICF, intracellular fluid.

21 Albumin Pharmacokinetics Normal Critical Illness

22 Factors Influencing Fluid Balance and Electrolytes in Critically Ill Patients Neourohormonal stimulation Hypoalbuminemia

23 Effect of Iso-oncotic Colloids The context sensitivity of volume effects of isooncotic colloids: while 6% hydroxethylstarch or 5% human albumin remain within the circulation to almost 100% if infused as a substitute during acute blood loss (left-hand column)29, the preparations vanish out of the vasculature to a large extent if applied as a hypervolaemic bolus (right-hand column). Jacob et al (2007, Lancet 369: )

24 Common Findings For Fluid Status In Critically ill Patients Overhydration with increased interstitial compartment fluid and decreased intravascular compartment Decreased albumin and intravascular colloid osmotic pressure Increased vascular permeability

25 Fluid Balance and Acute Kidney Injury Topics What s known in 2009? n Fluid Accumulation is associated with adverse outcomes n Pathophysiology of Fluid shifts in critical illness n Relationship of fluid accumulation to AKI

26 Fluid Balance and AKI Adapted From Pearson TA et al Circulation 2003

27 Fluid balance and Acute kidney Injury What is the relationship of fluid accumulation and AKI? n Marker of severity

28 Fluid accumulation and AKI Consequence (Marker) AKI Mortality Fluid overload

29 Fluid balance and Acute kidney Injury What is the relationship of fluid accumulation and AKI? n Marker of severity n Risk factor for AKI

30 Fluid accumulation and AKI Consequence Cause of AKI (Mediator) AKI Mortality Fluid overload AKI Fluid overload

31 Fluid resuscitation with colloids does not reduce mortality more than crystalloids in critically ill patients Study selection and assessment: Randomized controlled trials (RCTs) that compared colloids (dextran 70, hydroxyethyl starches, modified gelatins, albumin, or plasma protein fraction [PPF]) with crystalloids (isotonic or hypertonic) for volume replacement in criticallyill patients, including those with trauma or burns, having surgery,or with such conditions as complications of sepsis. Crossovertrials and trials in neonates or preoperative, elective surgicalpatients were excluded. 58 RCTs and 6 quasi-rcts met the selection criteria. 8 RCTs reported adequate allocation concealment, 38 had no loss to follow-p, and blinding was not well reported. Outcome: Mortality. Perel P, Roberts I. Colloids versus crystalloids for fluid resuscitation in critically ill patients. Cochrane Database Syst Rev. 2007;(4):CD

32 Schortgen et al: The risk associated with hyperoncotic colloids in patients with shock Intensive Care Med (2008) 34: Objective: This study assessed the risk of renal adverse events in patients with shock resuscitated using hypooncotic colloids, artificial hyperoncotic colloids, hyperoncotic albumin or crystalloids, according to physician s choice. Participants and setting: International prospective cohort study including 1,013 ICU patients needing fluid resuscitation for shock. Patients suffering from cirrhosis or receiving plasma were excluded. Measurements and results: Influence of different types of colloids and crystalloids on the occurrence of renal events (twofold increase in creatinine or need for dialysis) and mortality was assessed using multivariate analyses and propensity score.

33 Schortgen et al: The risk associated with hyperoncotic colloids in patients with shock Intensive Care Med (2008) 34: Objective: This study assessed the risk of renal adverse events in patients with shock resuscitated using hypooncotic colloids, artificial hyperoncotic colloids, hyperoncotic albumin or crystalloids, according to physician s choice. Participants and setting: International prospective cohort study including 1,013 ICU patients needing fluid resuscitation for shock. Patients suffering from cirrhosis or receiving plasma were excluded. Measurements and results: Influence of different types of colloids and crystalloids on the occurrence of renal events (twofold increase in creatinine or need for dialysis) and mortality was assessed using multivariate analyses and propensity score. Incidence of renal and nonrenal adverse events in the 822 study patients. Crystalloids Patients receiving crystalloids only within the first 8 days of shock resuscitation or before renal adverse event occurrence. Hypooncotic colloids Patients receiving gelatins and/or 4% albumin within the first 8 days of shock resuscitation or before renal adverse event occurrence. Artificial hyperoncotic colloids Patients receiving dextrans and/or hydroxyethylstarches within the first 8 days of shock resuscitation or before renal adverse event occurrence. Hyperoncotic albumin Patients receiving 20 or 25% albumin within the first 8days of shock resuscitation or before renal adverse event occurrence. Renal event Renal dysfunction

34 Fluid balance and Acute kidney Injury What is the relationship of fluid accumulation and AKI? n Marker of severity n Risk factor for AKI n Mediator of adverse outcomes

35 Fluid accumulation and AKI Consequence Cause AKI Mortality Fluid overload AKI Fluid overload Mortality

36 Fluid Balance and AKI Prowle, J. R. et al. Nat. Rev. Nephrol. 6, (2010);

37 Fluid Balance and AKI Prowle, J. R. et al. Nat. Rev. Nephrol. 6, (2010);

38 Fluid Balance and AKI Prowle, J. R. et al. Nat. Rev. Nephrol. 6, (2010);

39 Distant Effects of Acute Kidney Injury Scheel et al: Kid Int 2008

40 Fluid Balance and Acute Kidney Injury Practical Implications Fluid Accumulation is common

41 1. Fluid accumulation is common Fluid administration for resuscitation and compartmental shifts Response to Fluid Administration

42 2. Fluid Accumulation is common Fluid and Electrolyte Balance Post Major Surgery Intake Daily Requirements Post-Op Post-Op Output Fluid (ml/day) ml/kg 8000 Urine ( ml/day) 1000 Insensible Loss 1000 Sodium ( mmol) mmol/kg Potassium (mmol) 1 mmol/kg Nitrogen (mmol) (catabolism) Other solutes (mmol) mosmoles ml positive fluid balance, 3000 mosmoles positive balance Requires 6 litres of urine to clear sodium + N 2 (500 mosm/l maximum concentration) I liter of normal Saline = 154 mmol of Na = 9G of salt which is >2 fold more than daily requirement!

43 Fluid Balance and Acute Kidney Injury Practical Implications Fluid Accumulation is common Fluid accumulation may go unrecognized

44 2. Fluid Accumulation has consequences: it may be missed or unaccounted for Definitions Fluid Balance: Daily difference in all intakes and outputs n Generally does not include insensible losses n May not correlate with weight n Should include dialysis fluid removal Cumulative fluid balance: Sum total of fluid accumulation over a set period of time n More important and relevant to assess change over time n Amount and duration key parameters associated with outcome n Response to treatment Fluid Overload: Cumulative fluid balance expressed as a percent of body weight at baseline (ICU admission) n Cut off of 10% has been associated with increased mortality

45 Alsous et al: Negative Fluid Balance Predicts Survival in Patients With Septic Shock* CHEST 2000; 117: ) Daily Fluid Balance Cumulative Fluid Balance Fluid balance in subgroups of 36 patients with septic shock. Top, A: net fluid balance (inputs-outputs) in patients who survived is shown. Middle, B: net fluid balance in patients who died is shown. Bottom, C: the aggregate daily mean (6 SE) values comparing those who survived vs those who died are shown.

46 Macedo et al: Fluid Accumulation Underestimates Severity of Acute Kidney Injury in Critically-ill Patients Critical Care patients in PICARD database (n=618) with consecutive increase in serum creatinine over 3 to 7 days prior to any dialysis Correction of Creatinine Values for Fluid Balance Creatinine adjusted = serum creatinine x correction factor Correction factor = [hospital admission weight (kg) x Σ (daily fluid balance)]/ hospital admission weight x 0.6

47 Fluid Accumulation Underestimates Severity of Acute Kidney Injury In Critically-ill Patients Etienne Macedo, MD 1, Josée Bouchard, MD 1, Sharon Soroko, MS 1, Glenn M. Chertow, MD, MPH 2, Jonathan Himmelfarb, MD 3, T. Alp Ikizler, MD 4, Emil P. Paganini, MD 5, Ravindra L Mehta, MD 1. Program to Improve Care in Acute Renal Disease (PICARD) study Daily underes-ma-on Adj scr crude scr Crude scr Underes-ma-on of Progression Reference scr (Adj scr reference) (crude scr reference) Reference scr Progression in Severity

48 Fluid Balance and Acute Kidney Injury Practical Implications Fluid Accumulation is common Fluid accumulation may go unrecognized Fluid accumulation has consequences

49 3. Fluid Accumulation has consequences: HAGIE Hospital acquired generalised interstitial edema Minimised by Fluid restriction and colloid resuscitation to appropriate haemodynamic targets Lyons W. Crit Care Med 2000 Lyons W. J Trauma 2002

50 3. Fluid Accumulation has consequences: Excess resuscitation with crystalloids may be harming patients Increased incidence of ACS Secondary ACS is definitely iatrogenic Crystalloid fluids are distinct and active medications

51 Intra Abdominal Hypertension and ACS Pre-disposing Factors Common Etiological Factors

52 Marjanovic et al: Impact of Different Crystalloid Volume Regimes on Intestinal Anastomotic Stability Ann Surg 2009;249: ) Design: Experimental study in Rats Twenty-one rats were randomly assigned to 3 experimental groups (n 7 rats/ group): control group CO (9 ml kg1 h1 crystalloid infusion), volume restriction group V () (3 ml kg1 h1), and animals with volume overload V () (36 ml kg1 h1). After midline incision, all animals received the corresponding infusion for a 30minute period. Infusion was continued for further 30 minutes whereas an end-to-end small bowel anastomosis was performed 15 cm proximal to the Bauhin valve with 8 nonabsorbable interrupted inverting sutures. At reoperation on the 4th postoperative day, the anastomotic segment was dissected and the bursting pressure mmhg was measured. Outcomes: Hospital Mortality

53 Consequences of Fluid Overload The gut origin of sepsis hypothesis, with bacterial translocation as a potential stimulus for ongoing inflammation. Gatt et al Aliment Pharmacol Ther 2007, 25,

54 Consequences of Fluid Overload The Interactions between the pancreas and intestine during sever acute pancreatitis with monitoring and interventions used in its treatment Flint et al: HPB 2003, 5:: 69-85

55 Consequences of Fluid Overload Total fluid input (a), urinary output (b), urinary Na excretion (c) and change in body weight (d) in patients receiving 3 litres water and 154 mmol Na/d (standard group; &) or 2 litres water and 75 mmol Na/d (restricted group; m) after uncomplicated colonic surgery. Values are means with their standard errors represented by vertical bars. Significance values for differences between groups were: (a) P< , (b) P = 0.06 (NS), (c) P= 0.15 (NS), (d) P < Lobo et al Lancet 2002

56 Cumulative Water and Na Balance (Days 0-4) Standard Group Water balance (l) 7.2 ( ) Restricted Group 3.7 ( ) P value < Sodium balance (mmol) 747 ( ) 82 ( ) Median (IQR) Lobo et al, Lancet 2002

57 Gastric Emptying Time Solid phase gastric emptying time T 50 (min) N = 10 Standard Group 10 Restricted Group Liquid phase gastric emptying time T 50 (min) N = 10 Standard Group 10 Restricted Group P=0.028 P=0.017 Lobo et al, Lancet 2002

58 Lobo: Proceedings of the Nutrition Society (2004), 63, Consequences of Fluid Overload Hypothesis proposed for the effects of salt and water overload on gastrointestinal function.

59 Abdominal Compartment Syndrome Modified from Saggi B et al. J of Trauma :

60 Abdominal Compartment Syndrome Pathophysiology Modified from Saggi B et al. J of Trauma :

61 Doty JM et al: Effect of increased renal venous pressure on renal function.j of Trauma 1999, 47:1000-3

62 Vidal et al: Incidence and clinical effects of intra-abdominal hypertension in critically ill patients (Crit Care Med 2008; 36: ) Objective: The objective of this study was to determine the epidemiology and outcomes of intra-abdominal hypertension in a heterogeneous intensive care unit population. Design: This was a prospective cohort study. Setting: This study was conducted at a medical surgical intensive care unit in a university hospital. Patients: Study patients included all those consecutively admitted during 9 months, staying >24 hrs, and requiring bladder catheterization. Methods: IAH was defined as IAP >12 mm Hg. ACS was defined as IAP >20 mm Hg plus >1 new organ failure. Main outcome measure was hospital mortality.

63 Vidal et al: Incidence and clinical effects of intra-abdominal hypertension in critically ill patients (Crit Care Med 2008; 36: ) Objective: The objective of this study was to determine the epidemiology and outcomes of intra-abdominal hypertension in a heterogeneous intensive care unit population. Design: This was a prospective cohort study. Setting: This study was conducted at a medical surgical intensive care unit in a university hospital. Patients: Study patients included all those consecutively admitted during 9 months, staying >24 hrs, and requiring bladder catheterization. Methods: IAH was defined as IAP >12 mm Hg. ACS was defined as IAP >20 mm Hg plus >1 new organ failure. Main outcome measure was hospital mortality.

64 Vidal et al: Incidence and clinical effects of intra-abdominal hypertension in critically ill patients (Crit Care Med 2008; 36: ) Objective: The objective of this study was to determine the epidemiology and outcomes of intra-abdominal hypertension in a heterogeneous intensive care unit population. Design: This was a prospective cohort study. Setting: This study was conducted at a medical surgical intensive care unit in a university hospital. Patients: Study patients included all those consecutively admitted during 9 months, staying >24 hrs, and requiring bladder catheterization. Methods: IAH was defined as IAP >12 mm Hg. ACS was defined as IAP >20 mm Hg plus >1 new organ failure. Main outcome measure was hospital mortality.

65 Relationship between CV parameters and renal function Objective To determine whether venous congestion, rather than impairment of cardiac output, is primarily associated with the development of worsening renal function in patients with advanced decompensated heart failure. Methods Observational prospective study 145 consecutive patients admitted with acute decompensated CHF treated with intensive medical therapy guided by PAC were studied. Worsening renal function defined as an increase of serum creatinine 0.3 mg/dl during hospitalization. Mullens W et al J Am Coll Cardiol 2009;53:589 96

66 3. Fluid Accumulation has consequences: Impact of CVP on glomerular hemodynamics J Am Coll Cardiol 2009;53:597 9

67 Is this a common problem? All trauma admissions Trauma ICU admissions Shocked trauma ACS 0.09 % 0.7 % 8 %

68 Is this a common problem? Malbrain. Intensive Care Med 2004; 30:

69 Post-Injury ACS 77 patients - damage control surgery 77 36% developed ACS Raeburn. AmJSurg 2001; 182:

70 Post-Injury ACS Raeburn. AmJSurg 2001; 182:

71 Fluid Balance and Acute Kidney Injury Practical Implications Fluid Accumulation is common Fluid accumulation may go unrecognized Fluid accumulation has consequences Primary Prevention

72 4. Fluid management: Primary Prevention Body Compartment Alterations are Common

73 Two Questions Does my patient need parenteral fluid? Why does my patient need parenteral fluid?

74 Why? To correct an intravascular or extracellular volume deficit Resuscitation To replace ongoing losses Replacement To supply the daily needs - Maintenance

75 2. Fluid Accumulation is common Fluid and Electrolyte Balance Post Major Surgery Intake Daily Requirements Post-Op Post-Op Output Fluid (ml/day) ml/kg 8000 Urine ( ml/day) 1000 Insensible Loss 1000 Sodium ( mmol) mmol/kg Potassium (mmol) 1 mmol/kg Nitrogen (mmol) (catabolism) Other solutes (mmol) mosmoles ml positive fluid balance, 3000 mosmoles positive balance Requires 6 litres of urine to clear sodium + N 2 (500 mosm/l maximum concentration) I liter of normal Saline = 154 mmol of Na = 9G of salt which is >2 fold more than daily requirement!

76 4. Fluid management: Primary Prevention Hypothetical curve of the risk of fluid therapy-related complications versus volume of fluid infused Hilton et al: MJA 2008; 189:

77 4. Fluid management: Primary Prevention Hypothetical risk versus volume replacement curves for an individual patient in different clinical scenarios Curve A: Low-risk clinical context, such as elective colonoscopy, where optimal fluid requirements are minimal, and the patient can tolerate significant variations in volume replacement. Curve B: The same patient in a slightly higher-risk context, such as elective colectomy. The volume for optimal fluid replacement is likely to be higher than in Scenario A, and the tolerance for error slightly lower, given the larger volume and pathophysiological changes associated with surgery. Curve C: The same patient in a highrisk clinical context, such as urgent laparotomy for intra-abdominal sepsis and hypotension. Fluid requirements are likely to be high, and the patient is unlikely to tolerate significant deviations from this amount. Hilton et al: MJA 2008; 189:

78 Restrictive Post-Op Fluid Regimens Hilton et al: MJA 2008; 189:

79 BUNDGAARD-NIELSEN et al: Liberal vs. restrictive perioperative fluid therapy a critical assessment of the evidence Acta Anaesthesiol Scand 2009; 53: In the seven randomized studies identified, the range of the liberal intraoperative fluid regimen was from 2750 to 5388 ml compared with 998 to 2740ml for the restrictive fluid regimen. The period for fluid therapy and outcome endpoints were inconsistently defined and only two studies reported perioperative care principles and discharge criteria. Three studies found an improved outcome (morbidity/hospital stay) with a restrictive fluid regimen whereas two studies found no difference and two studies found differences in the selected outcome parameters.

80 BUNDGAARD-NIELSEN et al: Liberal vs. restrictive perioperative fluid therapy a critical assessment of the evidence Acta Anaesthesiol Scand 2009; 53:

81 5. Fluid Management: Secondary Prevention Fluid management needs to be dynamic Sodium and water over load may be an inevitable consequence of the resuscitation process. Septic patients in the ICU gain as much as 12.5 L of body water during the first two days of resuscitation. It may take up to 3 weeks for patients to excrete this excess load. Plank et al, Ann Surg 1998

82 Early goal-directed therapy in the treatment of severe sepsis and septic shock Rivers et al: N Engl J Med 2001 Nov 8;345(19):

83 Murphy et al: The Importance of Fluid Management in Acute Lung Injury Secondary to Septic Shock. CHEST 2009; 136: Design: Single Center retrospective analysis of ICU patients Patients: 212 pts with Acute lung injury (ALI) within 72 hrs of sepsis Comparisons: Adequate initial fluid resuscitation (AIFR) administration of an initial fluid bolus of > 20 ml/kg prior to and achievement of a central venous pressure of > 8 mm Hg within 6 h after the onset of therapy with vasopressors. Conservative late fluid management (CLFM) was defined as even-to negative fluid balance measured on at least 2 consecutive days during the first 7 days after septic shock onset. Outcomes: Hospital Mortality

84 Rivers NEJM 2006

85 Murphy et al: The Importance of Fluid Management in Acute Lung Injury Secondary to Septic Shock. CHEST 2009; 136: Daily Fluid Balance Cumulative Fluid Balance

86 4. Fluid Management: Secondary Prevention Murphy et al: The Importance of Fluid Management in Acute Lung Injury Secondary to Septic Shock. CHEST 2009; 136: Design: Single Center retrospective analysis of ICU patients Patients: 212 pts with Acute lung injury (ALI) within 72 hrs of sepsis Comparisons: Adequate initial fluid resuscitation (AIFR) administration of an initial fluid bolus of > 20 ml/kg prior to and achievement of a central venous pressure of > 8 mm Hg within 6 h after the onset of therapy with vasopressors. Conservative late fluid management (CLFM) was defined as even-to negative fluid balance measured on at least 2 consecutive days during the first 7 days after septic shock onset. Outcomes: Hospital Mortality

87 FACTORS INFLUENCING FLUID MANAGEMENT IN ACUTE LUNG INJURY Acute Inflammatory Insult Sepsis, pneumonia Aspiration, pneumonia Transfusion, or other Ebb Phase Sodium and water conservation; Hypovolemia, vasodilation Myocardial suppression; increased Metabolic demands; and impaired Tissue use of oxygen Organ dysfunction Acute lung injury EARLY GOAL- DIRECTED RESUSCITATION STRATEGIES First 6 hours Fluid mobilization and DiscontinuatIon of Mechanical ventilation Cuthberson DP Lancet 1942 Rivers EP NEJM 2001 Wiedeman NEJM 2006 Rivers EP NEJM 2006 CONSERVATIVE VS. LIBERAL FLUID STRATEGIES hours Established Acute Lung Injury Shock reversal and volume- Replete intravascular space; Avidity for water and sodium; Low plasma oncotic pressure Increased lung water Flow Phase Conservation of fluids, Diuresis, or both; close Monitoring of electrolytes And volume status Coexisting Conditions and Considerations Unresolved shock and Inflammation Renal failure Myocardial dysfunction Endocrinopathies, hypo Thyroidism, adrenal dysfunction Prolonged need for mechanical ventilation (increased Antidiuretic hormone) Preexisting hypertension (increased retention of sodium and water) ULTRAFILTRATION HEMOFILTRATION Impaired fluid mobilization and increased lung water Identification and treatment Of coexisting conditions

88 Fluid Removal on Dialysis Refill Rate Interstitial Space Capillary Membrane interface for NDF Vascular Space D i a l y z e r UFR

89 Influence of Modality on Fluid Overload Mean percentage fluid overload Days

90 Fluid Balance and Acute Kidney Injury Topics What s known in 2010? Practical Implications Future Directions

91 Fluid Management in RRT Time for Change? Fluid management integral for dialysis procedures. Marked variation in procedures and approaches for fluid management. Inadequate fluid removal quite common in ICU setting Fluid retention contributes to poor outcome Limitation is not in machine capacity for fluid removal but how we use the machines!

92 SVV to Guide Fluid Management in CRRT

93 SVV to Guide Fluid Management in CRRT

94 Fluid Management with CRRT What can we do? Need Strategy Utilize dialysis for fluid regulation instead of fluid removal only CRRT can continuously adjust fluid balance in critically ill patients Late utilization when fluid redistribution into large compartments has already occurred Initiate RRT at earlier time points to prevent fluid accumulation Develop guidelines based on demonstrated best practices Protocol based standardization of approach Recognize importance of fluid retention on outcome Implement calculators to track fluid accumulation and fluid overload

95 Key Issues in Fluid Regulation with Dialysis Areas for Investigation What biomarkers signal time when fluid redistribution is occurring? What is magnitude or volume retention when therapy should be started? Can dialysis add additional fluid regulation capacity to the compromised kidney and avoid deleterious effects of diuretics Can we provide a safety net to test and support fluid management strategies in patients with compromised renal function

96 Fluid Regulation: Optimizing Renal Support Summary Fluid management is an important and integral part of renal support with dialysis Wide variation in current approach to fluid management with dialysis Process of care may contribute to the lack of improvement in outcomes CRRT techniques can be adapted to achieve any given fluid balance and tailor the therapy to patient needs dynamically.

97 Acknowledgements Program to Improve Care in Acute Renal Disease (PICARD)* Study Group Cleveland Clinic Foundation, Cleveland, OH: Emil Paganini MD, Tracy Seifert RN, Michelle Garcia RN, Lydia Sweeney RN, Tom Greene PhD, Brett Larive MS Maine Medical Center, Portland, ME: Jonathan Himmelfarb MD, Stephanie Freedman RN, Rebecca McClellan RN UCSD Medical Center, San Diego, CA : Ravindra Mehta MD, Maria T. Pascual RN, Carmencita Gruta RN UCSF Medical Center, San Francisco, CA: Glenn Chertow MD, Susan Robertson RN Vanderbilt Medical Center, Nashville, TN: T. Alp Ikizler MD, Cathi Martin RD, Data Coordinating Center, San Diego, CA: Ravindra Mehta MD, Brandon Savage MD, Maria T. Pascual RN, Sharon Soroko MS Fluid Management Data Analysis: Josee Bouchard MD: University of Montreal

98 Research Group PICARD UCSD AKI research group Josee Bouchard, Rolando Claure, Sam Kuo, Yang Luo, Etienne Macedo, Rakesh Malhotra, Sharon Soroko, Guillermo Sanz, Jiandong Wei

99