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Assistant Professor of Medicine, Department of Pulmonary, Allergy and Critical Care, Emory University, Atlanta, Georgia; Section Head, Pulmonary and Critical Care Director, Medical and Coronary Intensive Care, Pulmonary and Critical Care Department, Grady Memorial Hospital, Atlanta, Georgia
The administration of intravenous fluids is one of the most common and universal interventions in medicine. Crystalloid solutions are the most frequently chosen, by far, with normal saline (NS) and lactated Ringer's (LR) both being frequent choices in the United States. Colloids are an alternative to crystalloids, with highly variable use depending on a myriad of clinical variables. Of interest, the choice of intravenous fluids has remained one of the most controversial subjects in critical care over the past half a century. Given the frequency that these medications are used with impunity in the daily practice of medicine, it is remarkable how few data exist confirming either the safety or the efficacy of these intravenous fluids. This article discusses the relative choices of intravenous fluids available both in the United States and elsewhere in the world as well as emerging data for both the safety and efficacy of the most commonly used solutions.
There are fundamental differences between colloids and crystalloids in their formulation. Crystalloids are predominately based on a solution of sterile water with added electrolytes to approximate the mineral content of human plasma. Crystalloids come in a variety of formulations, from those that are hypotonic to plasma to those that are isotonic or hypertonic. One of the most common formulations, .9% normal saline, was designed to approximate the mineral and electrolyte concentration of human plasma; however, there are substantial differences (see Table 1). A frequent alternative to normal saline is LR, which more closely mimics the electrolyte concentration of human plasma as well as having a small amount of lactate included.
| Solution | pH | Na+ | Cl- | K+ | Ca++ | Lactate | Glucose | Osmolality | Other |
|---|---|---|---|---|---|---|---|---|---|
| .9% normal saline | 5.0 | 154 | 154 | 0 | 0 | 0 | 0 | 308 | 0 |
| LR | 6.5 | 130 | 109 | 4 | 3 | 28 | 0 | 275 | 0 |
| 5% dextrose in water (D5W) | 4.0 | 0 | 0 | 0 | 0 | 0 | 50 g/L | 252 | 0 |
| .45% normal saline with dextrose (D51/2 NS) |
4.5 | 77 | 77 | 0 | 0 | 0 | 50 g/L | 406 | 0 |
| Albumin (5%) | 6.4-7.4 | 130-160 | 130-160 | < 1 | 0 | 0 | 0 | 309 | 50 g/L albumin |
| Albumin (25%) | 6.4-7.4 | 130-160 | 130-160 | < 1 | 0 | 0 | 0 | 312 | 250 g/L albumin |
| Hetastarch 6% | 5.5 | 154 | 154 | 0 | 0 | 0 | 0 | 310 | 60 g/L starch |
| Pentastarch 10% | 5.0 | 154 | 154 | 0 | 0 | 0 | 0 | 326 | 100 g/L starch |
| Dextran-40 (10% solution) |
3.5-7.0 | 154 | 154 | 0 | 0 | 0 | 0 | 311 | 100 g/L dextran |
| Dextran-70 (6% solution) |
3.0-7.0 | 154 | 154 | 0 | 0 | 0 | 0 | 310 | 60 g/L dextran |
| Haemaccel 3.5% | 7.4 | 145 | 145 | 5 | 6.25 | 0 | 0 | 293 | 35 g/L gelatin |
| Gelofusine | 7.4 | 154 | 125 | 0 | 0 | 0 | 0 | 308 | 40 g/L gelatin |
LR = lactated Ringer's
All electrolyte ions are expressed in meq/L.
Colloids are often based on crystalloid solutions, thus containing water and electrolytes, but have the added component of a colloidal substance that does not freely diffuse across a semipermeable membrane. For albumin, that colloidal substance is human serum albumin with a molecular weight of 69,000 d, which serves as the largest component of colloid osmotic pressure in human blood. As you can see from Table 1, albumin comes in either an isooncotic formulation (5%) or a hyperoncotic formulation (25%). Another common colloid formulation is that of the generically called hetastarches, which includes 6% hetastarch and 10% pentastarch. The colloidal substance in starches is derived from a polysaccharide that is incorporated in the fluid with a wide variety of molecular weights. Dextran solutions have a somewhat diverse incorporation of synthetic dextran proteins, whereas gelatins have a true gelatin component that has been synthesized to be biologically compatible. Gelatins are not available in the United States, and dextrans have found limited use after their introduction as a prophylactic agent against postoperative venous thrombosis.
It has long been presumed that the administration of each of the above listed solutions results in adequate volume resuscitation and is safe on the basis of their historical record of use. The primary recognized difference between crystalloid and colloid solutions is the ability of colloid solutions to maintain or improve colloid osmotic pressure for patients to whom they are administered, in comparison with crystalloid solutions in which colloid osmotic pressure may be reliably reduced through hemodilution. The major difference between colloids and crystalloids from a global or nonpatient perspective is that colloids are substantially more expensive than crystalloids.[1] Because of this difference in cost and a lack of data showing superiority, many hospitals and healthcare organizations have restricted the use of colloids in order to reduce pharmacy expenditures.
So, are both colloids and crystalloids safe and effective means of intravenous fluid resuscitation? Although this has been the most common assumption over the past 60 years, it may not be true. The safety of colloids was first questioned by a rudimentary meta-analysis performed by Velanovich[2] in 1989. Since that time, there have been a number of other more elegant systematic reviews that have similarly questioned the safety of colloids. The first of these were published in BMJ in 1998 in which one systematic review questioned the safety of colloids in general[3] and another questioned specifically the safety of albumin.[4] Both of these meta-analyses suggested that there was a small but statistically significant increase in the risk of death for patients who received colloids over crystalloids. Since that time, there has been a rigorous and more focused meta-analysis, including an assessment of potential morbid complications of colloid use, which found no difference in outcome among patients treated with colloids or crystalloids.[5] Finally, the largest meta-analysis to date specifically examined the use of albumin (as opposed to grouping all colloids) and again reported that there was no difference in outcome for patients treated with albumin compared with crystalloids.[6]
However, the questions regarding the safety of colloids remained in clinicians' minds and circulated in the literature. Based on these concerns, the Australia and New Zealand Intensive Care Society's Clinical Trials Group (ANZICS-CTG) designed and conducted one of the largest critical care trials in history.[7] The SAFE (Saline versus Albumin Fluid Evaluation) trial randomized 7000 critically ill patients requiring fluid resuscitation to receive isooncotic albumin or isotonic crystalloid. In this study, there was no overall difference in outcome according to whether patients received colloids or crystalloids (relative risk for death with colloid use = .99, 95% confidence interval .91-1.09, P = .87). However, the SAFE study investigators prospectively defined 3 important subgroups for specific analysis. Those patients who were traumatically injured and required fluid resuscitation appeared to be more likely to die if they received colloids (see Table 2), and this was statistically true for those patients with traumatic brain injury compared with trauma patients as a whole (relative risk for death = 1.62, 95% confidence interval 1.12-2.34, P = .009). This increased risk of death for traumatically injured patients is in contrast to noteworthy trends toward a reduction in death for severe sepsis patients who received colloids (relative risk = .87, 95% confidence interval .74-1.02).
| Outcome | Albumin | Saline | RR (95% CI) | P Value |
|---|---|---|---|---|
| Trauma | 13.6% | 10.0% | 1.36 (.99-1.86) | .06 |
| (81 of 596) | (59 of 590) | |||
| Severe sepsis | 30.7% | 35.3% | .87 (.74-1.02) | .09 |
| (185 of 603) | (217 of 615) | |||
| ARDS | 39.3% | 42.4% | .93 (.61-1.41) | .72 |
| (24 of 61) | (28 of 66) |
RR = relative risk; CI = confidence interval; ARDS = acute respiratory distress syndrome
If colloids are safe for administration to heterogeneous groups of critically ill patients, are the more favored crystalloid solutions even safer? Although there are very little data to confirm either the safety or efficacy of crystalloid solutions, a growing body of literature questions both of these qualities. It is well known that crystalloid solutions rapidly redistribute to the extracellular fluid compartment and thus require larger infusions than colloids to expand intravascular volume.[8] In addition, crystalloids predictably reduce serum protein concentrations and packed red cell volume. These changes not only impair intended improvements in intravascular volume, they may also increase the risk of tissue edema and compound the reductions in tissue perfusion. Furthermore, saline-based fluids contain a significant amount of chloride, which may influence bicarbonate homeostasis in the kidney and result in a hyperchloremic metabolic acidosis.[9] In fact, chloride is a significant determinant of renal blood flow,[10] and intravenous administration of normal saline solutions has been associated with delayed renal function.[11] Finally, the administration of hyperchloremic saline-based fluids to elderly surgical patients may exacerbate the metabolic acidosis associated with surgery and additionally impair gastric mucosal perfusion.[12]
As with all medicines that we prescribe, it appears that even common intravenous solutions carry a certain amount of risk that must be assessed against the presumed benefit when choosing among fluids for an individual patient. As more attention has been focused on fluid resuscitation and the consequences thereof, the science of fluid administration has been evolving very rapidly.[13] There are now crystalloid-based intravenous solutions that include ethyl pyruvate as a mediator to alter the inflammatory response, and thus improve survival in preclinical models of sepsis and shock.[14,15] New biological effects of colloids have been discovered such that albumin may improve antioxidant capacity in critically ill patients,[16,17] and starch solutions may favorably influence the microcirculation.[18] The ultimate clinical benefit of these basic science findings remains to be defined, although preclinical models have suggested that specific colloid administration may adequately modulate the inflammatory response to prevent the development of lung injury after shock.[19] In the meantime, certain colloid solutions, particularly albumin, are growing as products for niche use, with data either confirming or suggesting clinical improvements for conditions, such as spontaneous bacterial peritonitis,[20] ascites,[21] and acute lung injury.[22]
