Maria B. ALBUJA-CRUZ, MD ALBUMIN: OVERRATED. Surgical Grand Rounds

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1 Maria B. ALBUJA-CRUZ, MD ALBUMIN: OVERRATED Surgical Grand Rounds

2 ALBUMIN Most abundant plasma protein 1/3 intravascular 50% of interstitial SKIN Synthesized in hepatocytes Transcapillary escape rate COP regulates synthesis Vercueil,, A. Physiology, Pharmacology and Rationale for Colloid Administration for Maintenance of Effective Hemodynamic Stability in Critically Ill Patients. Transfusion Medicine Reviews, Vol19. No2, 2005

3 FUNCTIONS OF ALBUMIN Oncotic pressure Binding of substances Metabolic function inactivation Acid-base function Antioxidant function scavenging free radicals Anticoagulant effects Nicholson, J.P, The Role of Albumin in Critical Illness.. BJ Anaesth 2000; 85:

4 ALBUMIN AND CRITICAL ILL PATIENTS Critical illness alters lters distribution of albumin In intact vascular compartment vol. expansion In disease correlates poorly with COP Concentration decrease from early course Rate of synthesis is decreased Hypoalbuminemia is strongly associated with poor clinical outcomes Pulimood,, T. Debate: Albumin Administration Should be Avoided in Critically Ill. Crit Care 2000, 4:

5 HYPOALBUMINEMIA IN ACUTE ILLNESS A meta-analysis analysis of 90 cohort studies Odds of death 137% Odds of morbidity 89% Odds of prolonged ICU stay 28% Odds of increased resource utilization 66% Vincet JL, Hypoalbuminemia in Acute Illness: Is There a Rationale for Intervention?? Ann Surg.. Vol.237, No.3, , 334, 2003.

6 SHOULD WE TREAT HYPOALBUMINEMIA? A meta-analysis analysis of 9 prospective controlled trials on correcting hypoalbuminemia Inconclusive as to potential benefits No significant overall reduction in morbidity Vincet JL, Hypoalbuminemia in Acute Illness: Is There a Rationale for Intervention?? Ann Surg.. Vol.237, No.3, , 334, 2003.

7 ALBUMIN IN CRITICALLY ILL PATIENTS Meta-analysis analysis of 30 randomized controlled trials Hypovolemia RR of death 1.46 Burns RR of death 2.40 Hypo-albuminemia albuminemia 1.68 For every 17 critically ill patients treated with albumin there is one additional death No evidence that reduce mortality strong suggestion that might increase risk of death Cochrane Injuries Group Albumin Reviewers. Human Albumin Administration in Critically Ill Patients: Systematic review of Randomized controlled trial. BMJ Vol.317:235-40, 1998.

8 ALBUMIN IN CRITICALLY ILL PATIENTS Prospective, randomized controlled clinical trial. 61 severely ill, hypo-albuminemic patients. 27 severe sepsis; 36 post-op op patients with SIRS ml/day Human Albumin 20% ml/day 500ml/day Hydroxyethyl-Starch (HES) ml/day 1000ml/day HES ml/day 1000ml/day Normal Saline Veneman T, Human Albumin and Starch Administration in Critically Ill Patients: ts: A prospective Randomized Clinical Trial.. Wien Klin Wochnschr,, 2004, 1116/9-10: 10:

9 ALBUMIN IN CRITICALLY ILL PATIENTS Patients receiving albumin COP and serum albumin concentrations higher 30 d mortality rates Albumin group 8 out of 15 (53%) Saline group 5 out of 16 (31%) (p<0.07) Albumin group more pulmonary edema vs saline (p<0.05) Veneman T, Human Albumin and Starch Administration in Critically Ill Patients: ts: A prospective Randomized Clinical Trial.. Wien Klin Wochnschr,, 2004, 1116/9-10: 10:

10 CRYSTALLOIDS MAY PROMOTE PULMONARY EDEMA BECAUSE THEY LOWER COP? Protective role of COP diminish when permeability is increased Single-centre, prospective, randomized, single blinded clinical trial. They compared filling pressure-guided fluid challenges with saline and with the colloids gelatin 4%, HES6% and albumin 5% on their effects on pulmonary capillary permeability, EVLW, COP and LIS. Verheij,, J. Effect of fluid loading with saline or colloids on pulmonary permeability, edema and lung injury score after cardiac and major r vascular surgery. BJ Anaesth 96:21-30, 2005.

11 Fluid Challenge Protocol

12 CRYSTALLOIDS MAY PROMOTE PULMONARY EDEMA BECAUSE THEY LOWER COP? Results: More saline was infused COP increased in colloid group CO increased more in colloid group PLI and ELW were above normal in 60% and 30% no changes after fluid loading Oxygenation ratio improved in all groups LIS increased in colloid group Verheij,, J. Effect of fluid loading with saline or colloids on pulmonary y permeability, edema and lung injury score after cardiac and major vascular surgery. BJ Anaesth 96:21-30, 2005.

13 CRYSTALLOIDS MAY PROMOTE PULMONARY EDEMA BECAUSE THEY LOWER COP? Type of fluid used for vol. loading doses does not affect pulmonary permeability and edema 1 Pulmonary edema may thus be more dependant on hydrostatic forces than on COP in capillary leakage states 2 1 Verheij, J. Effect of Fluid Loading with Saline or Colloids on Pulmonary P Permeability, Edema and Lung Injury Score after Cardiac and Major Vascular Surgery. BJ Anaesth 96:21-30, Fuhong, S. Fluid Resucitation in Severe Sepsis and Septic Shock: Albumin, HES, Gelatin or Lactate-Does it really make a difference. SHOCK, Vol. 27, No.5, , 526, 2007.

14 SALINE VS ALBUMIN FOR FLUID RESUSCITATION IN ICU Multicenter,, randomized, double-blind blind trial 6997 patients 3497 Albumin 4% 726 died; 111 remained ICU; 793 remained in hospital 3500 Saline 729 died; 87 remained ICU; 848 remained in hospital Number of patient who had new single-organ or multiple organ failure was similar in the two groups The SAFE study Investigators. A Comparison of Albumin and Saline for Fluid Resuscitation in the Intensive Care Unit.. N Eng J Med, 350: , 2004.

15 SALINE VS ALBUMIN FOR FLUID RESUSCITATION IN ICU RR of death in patient of trauma in albumin group was Without trauma 0.96 Equivalent rates of death during 28 day study period Requirements for mechanical ventilation and renal- replacement therapy, time spent in the ICU and in the hospital equivalent In conclusion albumin and saline clinically equivalent The SAFE study Investigators. A Comparison of Albumin and Saline for Fluid Resuscitation in the Intensive Care Unit.. N Eng J Med, 350: , 2004.

16 COLLOID VS CRYSTALLOIDS FOR FLUID RESUSCITATION IN CRITICALY ILL PATIENTS Meta-analysis analysis of 53 randomized or quasi- randomized trials of colloids compared to crystalloids RR with albumin was 1.02 Result of this updated meta-analysis analysis NO EVIDENCE that colloids are superior to crystalloids Roberts I. Colloids vs Crystalloids for Fluid Resuscitation in Critically Ill Patients. Chochane Databese of Systematic Reviews, 2004

17 FLUID RESUSCITATION IN SEVRE SEPSIS AND SEPTIC SHOCK? If type of IV fluid impact on outcome in an animal model of septic shock Animals randomized to receive RL alone or combined with 20% albumin or 6% HES or gelatin alone Albumin and HES higher CO, O2 delivery and lower blood lactate. Choice of IV fluid DID NOT affect outcome

18 ALBUMIN IS A HAZARD TO THE WALLET 0.9% Sodium Chloride 1000ml $0.74 Lactate Ringer s $0.89 6% Hetastarch 500ml $ % Albumin 100ml $ % Albumin 500ml $39.98 UCHSC, Proposed Guidelines for Use of Plasma Volume Expanders and Plasma Oncotic Agents

19 CONCLUSIONS Difficult to justify the use of albumin to maintain serum albumin levels within normal rage without clinical evidence that improves patient outcome Efforts should be concentrated on correcting underlying cause of disease to reverse hypoalbuminemia Studies failed to show advantage of fluid resuscitation with albumin when compared with crystalloids

20 CONCLUSIONS Crystalloids do not increase risk of pulmonary edema Favorable effects in particular patients can not be excluded Synthetic colloids and crystalloids may offer an effective, cheaper and safe8 alternative Need of randomized double blinded stratified control studies Debunked pathophysiology myth:1:1.4

21 THANK YOU