Indicatins of salt free albumin

A brief presentation about the current evidence based medical knowledge about the use of salt free albumin . After finishing this presentation you might discover that a lot of our practice lacks a solid basis regarding the use of this expensive drug.

1. Indications of salt free albumin By Ahmed Adel Abdelhakeem Assistant lecturer , Internal medicine department , GI & Hepatology unit Asyut university hospital

2. Human albumin (HA) is widely used for volume replacement or correction of hypoalbuminaemia. The value of HA in the clinical setting continues to be controversial , and it is unclear whether in today's climate of cost consciousness, there is still a place for such a highly priced substance. It is therefore appropriate to update our knowledge of the value of HA.

3. CLINICAL PHARMACOLOGY The albumin concentration in plasma in healthy humans ranges between 33 and 52 g litre. Albumin is synthesized exclusively in the liver. The normal rate of albumin synthesis is ∼ 0.2 g kg body weight per day.

4. CLINICAL PHARMACOLOGY Albumin is responsible for 70-80% of the colloid pressure of normal plasma carrier of hormones, enzymes, medicinal products and toxins The total body albumin in a 70 kg man is estimated to be 350g, it has a half live of about 13-19 days with a turnover of approximately 15g per day

5. FUNCTIONS OF ALBUMIN

6. INDICATIONS Volume replacement in the perioperative period Neither benefit nor harm was shown when using HA to maintain hemodynamic stability in the perioperative period when compared with crystalloids or any other colloidal volume substitute. (1) If, in contrast, a newer synthetic colloid solution was used (Mw 200 kDa, MS 0.5; eight trials involving 299 patients ) (2) , there was no longer any statistically significant difference in comparison with HA.

7. INDICATIONS Volume replacement in intensive care unit patients The largest trial currently available included ∼7000 patients and used a prospective, randomized, double-blind design to compare volume substitution in intensive care patients with either crystalloid substitutes (saline solution) or HA 4% [Saline vs. Albumin Fluid Evaluation (SAFE) study ] (3) . No significant beneficial effect of HA was found with respect to either morbidity and mortality or days spent in the intensive care unit (ICU) or in hospital . International guidelines for the management of severe sepsis and septic shock (4) do not specifically recommend the use of HA for volume replacement for hemodynamic stabilization in this setting.

8. INDICATIONS Volume replacement in burn patients Burns are seen as a potential indication for administration of HA, but not in the first 24 h after burn trauma. Crystalloid solutions are preferred as volume replacement (5) .

9. INDICATIONS Volume replacement in trauma patients The use of HA to correct hypovolaemia in trauma patients has not been shown to have a significant benefit in survival when compared with other plasma substitutes. (6) (7) in patients with traumatic brain injury, a post hoc follow-up analysis of the data from the SAFE study showed a significantly increased mortality for the group treated with HA as opposed to the non-albumin-treated group (8)

10. INDICATIONS Volume replacement in hepatic surgery (including liver transplantation) Correction of hypovolaemia in patients undergoing major liver surgery or liver transplantation has long been considered an indication for using HA. However, such patients have also successfully been treated with synthetic colloids. There are no large-scale prospective trials (9) . In a prospective study of 40 patients after living related liver transplantation, patients were randomized to an HA group ( n =20), where 20% HA was given to maintain serum albumin level ≥3 g dl −1 , and a control group ( n =20), where there was no correction for serum albumin (10). Postoperative HA administration did not produce significant clinical benefits in these patients.

11. INDICATIONS Correction of hypoalbuminaemia in surgical or ICU patients reports confirmed that although hypoalbuminaemia is associated with increased mortality, the use of albumin in critically ill patients with a serum albumin concentration ≤25 g litre is not associated with reductions in mortality, duration of ICU stay or mechanical ventilation, or in the use of renal replacement therapy (11). Thus, there is limited evidence to justify the use of (hyperoncotic) HA for resuscitation or supplementation in these patients (11).

12. INDICATIONS Use of HA in undernutrition, malnutrition, and enteropathies/malabsorption syndrome No benefit for the administration of HA in undernutrition, malnutrition, and enteropathies / malabsorption syndrome has been shown. Its composition of amino acids which has a low ratio of some essential amino acids (tryptophan, methionine, and isoleucine) makes HA unsuitable for use in parenteral nutrition.

13. INDICATIONS Correction of hypoalbuminaemia in patients with liver cirrhosis In cirrhotic patients with ascites, there is some evidence that HA leads to a reduction in morbidity and mortality (12) (13). Three clinical situations have been described where the use of HA may be indicated: spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS), and post-paracentesis syndrome (PPS).

14. INDICATIONS Paracentesis in patients with liver cirrhosis Paracentesis for drainage of ascites without volume compensation is associated with the risk of developing PPS. The incidence of PPS is associated with a considerably higher risk of developing renal failure and an overall increased mortality (14) (15).

15. INDICATIONS Correction of hypoalbuminaemia in Nephrotic syndrome In nephrotic syndrome, albumin is lost via the kidneys. Compensation of the resulting hypoalbuminaemia is not useful as most of it is quickly eliminated again.

16. CONTRAINDICATIONS Albumin should be used with caution in conditions where hypervolemia and its consequences or hemodilution could represent a special risk for the patient. Examples of such conditions are : established allergy against HA Decompensated cardiac insufficiency Hypertension Esophageal varices Pulmonary edema Hemorrhagic diathesis Severe anemia Renal and post-renal anuria

17. CONCLUSION the widespread use of HA worldwide appears to be based on strong views rather than controlled study results. The wider use of HA should not be based on presumed potential benefits in selected patient groups .

18. CONCLUSION Systematic Reviews on albumin found that for patients with hypovolaemia , there is no evidence that albumin reduces mortality when compared with cheaper alternatives (16). These Reviews also showed that there is no evidence that albumin reduces mortality in critically ill patients with burns and hypoalbuminaemia . A meta-analysis of randomized, controlled trials showed that except in patients with ascites , the use of HA was not associated with significantly improved morbidity (17).

19. Effects of use of HA on risk ratio (RR) and confidence interval (CI) for morbidity in different clinical settings

20. REFERENCES Boldt J, Schöllhorn T, Mayer J, Piper S, Suttner S, The value of an albumin-based intravascular volume replacement strategy in elderly patients undergoing major abdominal surgery. Anesth Analg 2006;103:191-9 Wilkes MM, Navickis RJ, Sibbald WJ, Albumin versus hydroxyethyl starch in cardiopulmonary bypass surgery: a meta-analysis of postoperative bleeding. Ann Thorac Surg 2001;72:527-33. Finfer S, Bellomo R, Boyce N, SAFE Study Investigators. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med 2004;350:2247-56 Dellinger RP, Levy MM, Carlet JM, et al. ; International Surviving Sepsis Campaign. International guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008;36:296-327. Boldt J, Pabsdorf M . Fluid management in burn patients: results from a European survey—more questions than answers. Burns 2008;34:328-38. Technology Assessment: Albumin, Non-protein Colloid, and Crystalloid Solutions. Oak Book, IL, USA: University HealthSystem Consortium; 2000. Wilkes MM, Navickis RJ . Patient survival after human albumin administration—a meta-analysis of randomized controlled trials. Ann Intern Med 2001;135:149-64.

21. REFERENCES Myburgh J, Cooper J, Finfer S, et al. ; SAFE Study Investigators; Australian and New Zealand Intensive Care Society Clinical Trials Group; Australian Red Cross Blood Service; George Institute for International Health. Saline or albumin for fluid resuscitation in patients with traumatic brain injury. N Engl J Med 2007;357:874-84. Cammu G, Troisi R, Cuomo O, de Hemptinne B, Di Florio E, Mortier E . Anaesthetic management and outcome in right-lobe living liver-donor surgery. Eur J Anaesthesiol 2002;19:93-8. Mukhtar A, El Masry A, Moniem AA, Metini M, Fayez A, Khater YH . The impact of maintaining normal serum albumin level following living related liver transplantation: does serum albumin level affect the course? A pilot study. Transplant Proc 2007;39:3214-8. Myburgh JA, Finfer S . Albumin is a blood product too—is it safe for all patients? Crit Care Resusc 2009;11:67-70. Gentilini P, Casini-Raggi V, Di Fiore G, et al . Albumin improves the response to diuretics in patients with cirrhosis and ascites: results of a randomized, controlled trial. J Hepatol 1999;30:639-45. Sort P, Navasa M, Arroyo V, et al . Effects of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. N Engl J Med 1999;342:403-9. Gines P, Tito L, Arroyo V, et al . Randomized comparative study of therapeutic paracentesis with and without intravenous albumin in cirrhosis. Gastroenterology 1988;94:1493-502.

22. REFERENCES Moore KP, Wong F, Gines P, et al . The management of ascites in cirrhosis: report on the consensus conference of the International Ascites Club. Hepatology 2003;38:258-66. Alderson P, Bunn F, Li Wan Po A, et al . Human albumin solution for resuscitation and volume expansion in critically ill patients. Cochrane Database Syst Rev 2004;18:CD001208 Vincent JL, Navickis RJ, Wilkes MM . Morbidity in hospitalized patients receiving human albumin: a meta-analysis of randomized, controlled trials. Crit Care Med 2004;32:2029-38.

23. Thank you