Question 1

Compare and contrast 0.9% saline and 4% albumin.

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College Answer

It was expected answers would include a comparison of the composition, physicochemical features and relevant physiology. Many candidates failed to adequately describe the differences  in distribution across the body  compartments or differences in physical properties of both fluids.  In particular, how albumin is manufactured did not appear to be well understood by candidates.


The examiners complained about nobody knowing how albumin was manufactured. As this was a compare-and-contrast question that asked for the trainees to juxtapose albumin and saline in a tabulated answer, the implication is that they also expected some sort of details about the industrial production of saline. Fortunately, that's a fairly straightforward one-step process. Sodium chloride has a molar weight of 58.44 grams, which means all you need to do is weigh out 150mmol of it (8.77 grams) and add that to a litre of sterile water. Or, more likely, add 877 grams of it to a ton of sterile water and then package it into litre containers in an automated packing machine.

Name Normal saline 4% Albumin
Class Crystalloid fluid Colloid fluid
Chemistry Monovalent cation salt Isooncotic human protein solution, presented in isotonic saline as carrier fluid
Manufacture Industrial production line; 8.77g NaCl is added to sterile water and presented in a non-pyrogenic heat stable packaging Collected as whole blood donation or as part of plasma apheresis collection; separated by ethanol fractionation or by the chromatographic separation method.
Octanoate added as preservative. Pasteurised by heat treatment at 60 degrees for 10 hours
Routes of administration IV, subcutaneously, orally, or as a neb (plus multople others) IV only
Absorption 100% oral bioavailability; well absorbed Zero oral bioavailability; degraded into component peptides by digestive enzymes
Solubility pKa 3.09; good water solubility pKa 6.75; good water solubility
Distribution VOD=0.2L/kg, basically confined to the extracellular fluid
(thus: 25% remains intravascular, 75% becomes interstitial)
VOD = 0.07L/kg (effectively confined to the circulating volume); minimally protein bound
Target receptor As a resuscitation fluid, you could say that the target receptor is the baroreceptor Various molecules in the bloodstream bind and form complexes
Metabolism Not metabolised Metabolised mainly by the reticuloendothelial system
Elimination Elininated renally, where specific reabsorption mechanisms in the renal tubule regulate the rate of sodium and chloride excretion Minimal renal excretion, except in cases of protein-losing nephropathy. Most of it is degraded by macrophages; 10% is eliminated though the gut
Time course of action Half life is 20-40 minutes in healthy volunteers, longer in shock states and in mechanically ventilated patients (up to 8 hours) Albumin molecules have a half life of around 27 days; the volume effect lasts perhaps 6-12 hours, depending on the leakiness of capillaries
Mechanism of action Expands the extracellular fluid volume and changes the biochemistry of the body fluids Expands the extracellular fluid volume and changes the biochemistry of the body fluids
Clinical effects Volume expansion:
- by 25% of the infused volume, after 25-30 minutes
- below the circulatory reflex activation threshold
- effect is greater during the infusion (prior to redistribution)
Change in osmolality:
- minimal; unnoticed by osmoreceptors
Change in biochemistry:
- trivial sodium elevation (~0.5-.0 mmol/L)
- nontrivial chloride elevation (up to 3 mmol/L)
- decrease in bicarbonate and base excess (also up to 3 mmol/L)
Multiple roles, including oncotic, immunomodulatory and transport roles. Acts as a binding substrate for xenobiotics.
Volume expansion:
- Isoosmolar and isooncotic: infused volume should theoretically remain in the circulation for some hours
- This 500mml (10%) change may trigger circulatory reflxes, resulting in baroreceptor-mediated decrease in heart rate and some peripheral vasodilation
Change in osmolality:
- minimal; unnoticed by osmoreceptors (100ml of hypotonic saline carrier fluid is too small a volume)
Change in biochemistry:
- similar to the effects of infusion 500ml of isotonic saline (as this is the carrier fluid)
Single best reference for further information Griffel and Kaufman (1992) Griffel and Kaufman (1992)


CSL has a site which features the full product information on their 20% Albumex bottles.

For those of us crazed with the lonely lust for albumin, Theodore Jr. Peters offers a 432 page ode, entitled “All About Albumin: Biochemistry, Genetics, and Medical Applications”.

Matejtschuk, P., C. H. Dash, and E. W. Gascoigne. "Production of human albumin solution: a continually developing colloid." British journal of anaesthesia 85.6 (2000): 887-895.

Iguchi, Naoya, et al. "Differential effects of isotonic and hypotonic 4% albumin solution on intracranial pressure and renal perfusion and function." Critical Care and Resuscitation 20.1 (2018): 48.

Cohn, Edwin J., et al. "Preparation and Properties of Serum and Plasma Proteins. IV. A System for the Separation into Fractions of the Protein and Lipoprotein Components of Biological Tissues and Fluids1a, b, c, d." Journal of the American Chemical Society 68.3 (1946): 459-475.

Hahn, Robert G., and David S. Warner. "Volume kinetics for infusion fluids." The Journal of the American Society of Anesthesiologists 113.2 (2010): 470-481.

Reddi, Benjamin AJ. "Why is saline so acidic (and does it really matter?)." International journal of medical sciences 10.6 (2013): 747.

Hahn, Robert G. "Clinical pharmacology of infusion fluids." Acta medica Lituanica 19.3 (2012): 210-212.

Griffel, Martin I., and Brian S. Kaufman. "Pharmacology of colloids and crystalloids." Critical care clinics 8.2 (1992): 235-253.