Albumin Usage in Clinical Medicine: Tradition or Therapeutic?
Section snippets
Development of Albumin Solution
Edwin Cohn's development of a stable albumin solution during World War II was based on a fractionation scheme which was rapidly adopted—and adapted—by a number of pharmaceutical companies. Cohn never took a patent on his work. His technology quickly yielded other therapeutics including immunoglobulins and procoagulants such as fibrinogen. Albumin, however, remained the mainstay product of the plasma protein industry for decades and is claimed to be crucial for its viability.2 That being the
Reflections on the Manufacture of Albumin
Albumin is a biological therapeutic, manufactured from an inherently variable source material using a variety of purification techniques. Despite the remarkable longevity of the Cohn process as a basic manufacturing chemistry for nearly 70 years, manufacturers have evolved variations to it to optimize protein yields, stability, and access to more proteins. In addition, other methods of protein separation, notably filtration and chromatography, have been introduced which have increased the
Physiology of Fluid Balance
The distribution of water in the different fluid compartments of the body and its alteration with the infusion of different fluids is shown schematically in Figure 2. Its passage between the intravascular and interstitial space is governed by Starling's hypothesis, summarized in the equation:in which filtration across the vascular endothelium is driven by capillary hydrostatic pressure Pc and interstitial protein osmotic pressure πi counteracted by an absorptive force exerted
Fluid Therapy in Hypovolemia
While most internal organs can lose more than 50% of their function before organ failure is apparent, loss of only 30% to 40% of the blood volume can result in life-threatening circulatory failure,34 and even minor degrees of hypovolemia can cause ischemia and organ dysfunction.35 The first recognition that loss of the fluid part of the blood led to hypovolemic shock was by William O'Shaughnessy during the English cholera outbreak of 1830, who suggested restoring the blood volume through
Crystalloids VERSUS Colloids
The expansion of the intravascular volume by crystalloid and colloid described in Figure 2 takes a significant time to reach equilibrium. The fluid balance equilibrium shown ignores the 60% of total body albumin which is in the interstitial space. In normal subjects, about 6 g of albumin move from the intravascular to the interstitial space every hour, returning to the lymphatic system. Since each g of albumin binds about 18 grams of water, this results, theoretically, in a fluid circulation of
Albumin—Meta-analyses and Trials
Discrepancies between MAs and subsequent RCTs have been noted,62 and assessment of individual trials as a guide to treatment of specific patient groups has been recommended.63 Horwitz64 has reviewed the factors contributing to conflicting results between RCTs addressing identical outcomes, and has commented on the effect of patient heterogeneity in affecting results. Such heterogeneity may be compounded in MAs and evaluation of individual trials is again recommended. The most recent iteration
Albumin as a Drug
Albumin clearly has important physiological functions, and hypoalbuminemia is strongly associated with poor clinical outcomes.76 This does not translate into evidence that albumin infusion results in improvements, as assessed through MA.8 The SAFE study showed similar outcomes irrespective of patients' baseline serum albumin concentration.77 In the majority of etiologies underpinning hypoalbuminemia, low albumin concentrations are a marker, not a cause, of the underlying disease.
Despite this,
Albumin's Future
Controversy regarding the role of albumin solutions in clinical therapeutics continues to reign. This is the result of an evidence base for the therapies which, in this author's view, has the following characteristics:
- 1.
It is flimsy due to a long period of therapeutic complacency, based on the dramatic results achieved in war time trauma, which led to an era of unquestioned belief in the role of albumin solutions as a natural, universal colloid.
- 2.
Once the era of evidence-based medicine started to
Conclusions
Albumin has had a history in which complacency has been succeeded by controversy, to be succeeded by the current era of active investigation. Enhanced recognition of the physiological complexity of the processes in which albumin is involved; appreciation of the need to target albumin therapies to appropriate patient groups and sub-groups and an awareness of the variability of albumin preparations should contribute to a new paradigm for this modality. Rather than a passive—and expensive—expander
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Conflict of interest: The author provides contractual services for the Plasma Protein Therapeutics Association, which represents the manufacturers of plasma products, including albumin, which operate on a profit basis.