What is the Role of Albumin in Sepsis? An Evidenced Based Affair. Justin Belsky MD PGY3 2/6/14

Transcription

1 What is the Role of Albumin in Sepsis? An Evidenced Based Affair Justin Belsky MD PGY3 2/6/14

2 Microcirculation

3 Capillary Leak in Sepsis

4 Asking the RIGHT Question Does albumin have a MORTALITY BENEFIT in septic patients? Does albumin improve HEMODYNAMICS in septic patients? What does DOCTOR RIVERS say?

5 Albumin Negatively charged, 585 amino acids Most abundant plasma protein (60%) 60% extravascular, 40% intravascular Synthesis Only in the liver Not stored, secreted immediately in portal circulation

6 Function Osmotic pressure 80% of colloid oncotic pressure (COP) High concentration/molecular weight Negative charge 12.5 grams of albumin = 450cc redistribution of fluid into plasma

7 Functions Anti-oxidant ROS Scavenger Anti -oxidant Reduces pro-inflammatory cytokines TNF-a Binding of Substrates Acid/Base Buffer Responsible for half of anion gap Decrease in albumin by 1 g dl - 1 can increase bicarb by 3.4 mmol litre -1 and decrease anion gap by 3.

8 Albumin Concentrations/Cost % = grams/100ml Two concentrations 25% 25%/100ml = 25 grams/100ml 50 ml = 12.5 grams Cost = $ % 5%/100ml = 5 grams/100ml 250ml bottles = 12.5 grams Cost = $ L NaCl = $10.00

9 How much would it cost? 25 grams albumin/day x 10 days = $700

10 Albumin How many grams of albumin are in a 50 ml bottle of 25% albumin?

11 Is Albumin Safe to Use?

12 9 large worldwide suppliers Reported Adverse Events ~100 million 40 gram dosages 3.82 x 10 6 kg Albumin 99 non fatal events reported 24 fatal events reported No deaths probably related 5 possibly related The incidence of fatal serious adverse events possibly related to albumin was 5.24 per 10 8 doses

13 Contraindicated in TBI

14 Hypoalbuminemia = Bad Meta-Analysis 291,433 patients Each 10-g/L decline in serum Increased mortality 137% Increased morbidity 89% Increased ICU stay 28% Increased hospital stay 71%

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16 Hydroxyethyl Starch Non Ionic Volume Expander Controversy with Joachim Boldt

17 Fluid resuscitation in the ICU with either 6% HES 130/0.42 (Tetraspan) or Ringer s acetate at a dose of up to 33 ml per kilogram of ideal body weight per day. Any additional used Lactated Ringers. 2012

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19 JAMA 2013

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21 Look at the DATA

22 groups Trauma ARDS Severe Sepsis

23 SAFE TRIAL >18 y/o Australia and New Zealand Admitted to ICU Physician deemed required IV fluids Maintain or increase volume Excluded Cardiac surgery, liver transplantation, burns

24 SAFE TRIAL Randomized Remaining ICU fluid 4% Albumin Normal Saline 6997 total patients 3,500 NS 3,497 Albumin

25 Outcomes Primary Outcome Measure Death at 28 days Secondary Outcome Measures 28 day survival time Number of new organ failures Duration of mechanical ventilation Duration of renal replacement therapy Duration of ICU and hospital LOS

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27 Fancy Statistics 2010 Multivariate logistics analysis Adjust for baseline factors 919/1,218 (75.5%) ADJUSTED ODDS RATIO 0.71 (95% CI , p = 0.03)

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29 Hemodynamics MAP = Same Lower HR Day 1,3 Higher CVP days 1-3

30 Pros Multicenter Randomized control trial Double blinded

31 Cons ICU PATIENTS Just a little too late? Capillary leak What if this started in the ED? All or nothing ALBUMIN OR NaCl ONLY

32 SAFE TRIAL Conclusions Fluid administration in the ICU with albumin versus NS for patients with severe sepsis improves 28 day mortality rates and hemodynamics

33 NOTE: No manuscript available at time of presentation, Slides taken from Critical Care Forum, Toronto 2013

34 How many grams of albumin is this???

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42 Crit Care Med 2011

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44 Favors Albumin Favors Control 17 RCT, OR 0.82 (95% CI , p = 0.047) Conclusion = Mortality benefit with albumin

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46 9 Randomized control trials reporting mortality Excluded pediatrics Excluded Joachim Boldt studies

47 9 trials measured mortality 1,455 patients P = 0.11 RR of mortality 0.90 (95% CI )

48 Conclusion Does albumin have a MORTALITY BENEFIT in septic patients? Safe Trial Yes, in 28 day mortality rate in severe sepsis OR 0.71, 95% CI of , p = 0.03 ALBIOS Yes, in 90 day mortality rate ONLY in septic shock patients Only looked at hypoalbuminemia patients P = Meta Analysis 17 RCT Yes, OR 0.82 (95% CI , p = RCT No difference (P = 0.11) But 95% CI ( )

49 Conclusion Does albumin improve HEMODYNAMICS in septic patients? SAFE Trial Lower HR day 1,3 Higher CVP 1-3 ALBIOS Increased MAP Increased CVP

50 2013 Surviving Sepsis Guidelines Consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) Level 2: Evidence obtained from well-designed controlled trials without randomization. Level C: At least fair scientific evidence suggests that there are benefits provided by the clinical service, but the balance between benefits and risks are too close for making general recommendations. Clinicians need not offer it unless there are individual considerations. Will likely change after ALBIOS Trial is published.

51 Future Research No large studies in the ED

52 Final Thoughts Do no harm Find me a study - TBI $$$ Avg septic shock = $171,000 $700, 25 g x 10 days Who I would give Albumin to in the ED ALL SEPTIC PATIENTS grams severe sepsis grams septic shock

53 Questions?