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The Journal of TRAUMA Injury, Infection, and Critical Care

Crystalloids and Colloids in Trauma Resuscitation: A Brief Overview of the Current Debate
Sandro B. Rizoli, MD, PhD, FRCSC
Background: Controversy regarding crystalloids or colloids for resuscitation has existed for over five decades, and large numbers of clinical trials have failed to resolve the controversy. In fact, the limitations of these studies have intensified the debate. This overview aims to revisit the debate of fluid resuscitation in trauma patients by critically appraising the metaanalyses on the subject. Methods: This study was a critical analysis of six meta-analyses found by MEDLINE search. Results: Overall, the choice of fluid may have a small or no effect on mortality. In trauma, the use of colloids is associated with a trend toward increased mortality. Conclusion: There is an urgent need for well-designed clinical trials. Because of many limitations, meta-analysis should be
interpreted with caution, possibly as hypothesis generating. However, even considering all weaknesses and nuances of interpretation, the meta-analyses reviewed suggest that trauma patients should continue to be resuscitated with crystalloids. Key Words: Fluid resuscitation, Crystalloid, Colloid, Meta-analysis, Evidence-based medicine.
J Trauma. 2003;54:S82S88.

he controversy over choosing crystalloids or colloids for fluid resuscitation has existed for over five decades. Despite the fact that most physicians today prefer to make their therapeutic decisions on solid scientific evidence, it is indeed the vulnerability of the present evidence that intensifies the debate. A quick literature search on the subject results in a massive number of studies. In fact, there are enough studies to sustain 11 systematic reviews or metaanalyses or quantitative data synthesis (for this study, these terms are used interchangeably).111 However, the poor quality of the majority of the primary studies, which is subsequently imparted to the systematic reviews, does nothing to settle the matter. In practice, the use of colloid or crystalloid fluids varies widely across the globe depending on personal choices, clinical experience, availability, and cost.12 There are, however, other reasons behind this debate. Fluid administration is one of the most basic concepts in resuscitation and is also part of the daily routine of medically managing most hospitalized patients. Fluid resuscitation is also a very active area of both clinical and experimental investigation, with a continuous accumulation of new insights and data.13 Furthermore, topics that never completely vanish may prove to have merit, as demonstrated with the recent

reemergence of the use of steroids in septic shock or even hypertonic saline in fluid resuscitation.14 16 The goal of this article is to revisit the current debate regarding the choice between crystalloids and colloids for the resuscitation of trauma patients. This was done by exploring the evidence on this topic in meta-analyses, and by appraising their results and recommendations. The conclusion of this critical appraisal is that these systematic reviews should be interpreted with caution and that there is an urgent need for well-designed clinical trials in fluid resuscitation. When resuscitation of all critically ill patients is considered, the combined results of the meta-analyses suggest that the choice of fluid used for resuscitation has a small or no effect on mortality. In contrast, when only resuscitation of trauma patients is considered, the results are very similar and suggest that resuscitation with colloids carries an increased mortality. Crystalloids therefore should remain the fluid of choice for the resuscitation of trauma patients in hemorrhagic shock.


Most physicians in the developed world today begin resuscitating trauma patients according to the Advanced Trauma Life Support (ATLS) guidelines of the American College of Surgeons.17 The current ATLS guidelines call for an aggressive fluid resuscitation regimen that starts with a 2-L bolus of crystalloids in adults, preferably lactated Ringers (LR) solution. Resuscitation continues with repeated boluses of LR solution, blood, and a systematic search and repair of surgically correctable sources of hemorrhage.17 Crystalloids primarily fill the interstitial space; consequently, edema is an expected outcome of resuscitation according to the ATLS guidelines. To expand plasma volume, the classical axiom is that three times more volume of crystalloid is required than the volume of blood that was lost.17 Today, this ratio is questioned, and should probably be 7:1 or May Supplement 2003

Submitted for publication April 13, 2002. Accepted for publication May 21, 2002. Copyright 2003 by Lippincott Williams & Wilkins, Inc. From the Department of Surgery, Sunnybrook and Womens College Health Science Centre, University of Toronto, Toronto, Ontario, Canada. Presented at the Fluid Resuscitation in Combat Symposium, Defence and Civil Institute of Environmental Medicine, October 2526, 2001, Toronto, Ontario, Canada. Address for reprints: Sandro B. Rizoli, MD, PhD, FRCSC, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada; email: sandro. DOI: 10.1097/01.TA.0000064525.03761.0C


Crystalloids and Colloids in Trauma Resuscitation

result of resuscitation-associated morbidity and mortality and length of hospital stay. Furthermore, the low cost of resuscitation fluids compared with other routine pharmacologic interventions exerts no major impact in the surgeons choice of fluid, and colloids are used in the United States more often than recommended by the Consensus of the University Hospital Consortium.28,29

Table 1 Effect of Different Solutions on Plasma

Volume Expansion
Volume infused (mL) Type of Fluid Infused Plasma Volume Expansion (mL)

1,000 1,000 250 500 100 500

D5W lactated Ringers 7.5% hypertonic saline 5% albumin 25% albumin Pentastarch

100 250 1,000 375 450 500


Once the physician considers using colloid fluids, the next step is choosing between the different types. There are four basic types of colloids: albumin and the synthetic dextrans, gelatins, and starches. An overview of some of their most relevant characteristics is presented in Table 2. The prototypical colloid is albumin, which is synthesized in the liver and is responsible for 80% of the oncotic pressure of the plasma. Albumin is commercially available in heattreated preparations, dissolved in isotonic saline. Its colloid osmotic pressure is similar to the oncotic pressure of the plasma, and infusion of the 25% solution expands plasma volume four to five times the volume infused. Frequently mentioned disadvantages of albumin include its critical short supply, the fact that it is a blood product, the theoretical risk of transmitting unknown infectious particles (such as prions) and, like all other colloids, its cost. Of the synthetic colloids, dextran and gelatins are rarely considered for the resuscitation of trauma patients, especially in North America. Besides its plasma-expanding properties, dextrans have a powerful anticoagulant effect and have been used for the prevention of postoperative venous thrombosis and pulmonary embolism.30 The anticoagulant properties of dextrans have limited their indication for the resuscitation of trauma patients; however, small amounts have been successfully used to prolong the effect of hypertonic saline infusion.15 Gelatins are mostly unavailable in North America, and their modest and short-lived effectiveness in expanding plasma volume has decreased the enthusiasm for this type of colloid worldwide.30 The remaining option in colloids is hydroxyethyl starch (HES). Although in Europe there are several commercially available formulations, in North America the options are almost exclusively restricted to the high-molecular-weight hetastarch and pentastarch.31,32 Different from other colloids, the pharmacokinetics of each HES formulation is determined by its structure, which includes not only molecular weight but also degree of substitution (number of hydroxyethyl groups present divided by the quantity of glucose molecules) and C2/C6 hydroxylation rate. This group of HES synthetic colloids, especially pentastarch, is very attractive. The colloid osmotic pressure of 10% pentastarch is two times that of the oncotic pressure of the plasma and expands plasma volume 1.5 times the volume infused. Besides their effectiveness in expanding plasma volume, they are readily available, have an unlimited supply, carry no risk of transmitting infectious disease, have minimal S83

even 10:1, because of the decreased colloid osmotic pressure secondary to decreased serum protein concentration from hemorrhage, capillary leaks, and crystalloid replacement.18 Table 1 provides a good approximation of how much of the total volume of crystalloids infused leaks into the extravascular compartments (Table 1). Tissue edema might become an important consideration, especially when dealing with head injury patients where dilutional hypo-osmolarity may worsen brain edema and impact on mortality.19 The dilutional decrease in colloid osmotic pressure by crystalloids may also worsen pulmonary edema, thus impairing gas exchange.18 It also causes endothelial and red blood cell edema, impairing microcirculation and decreasing surface area for tissue oxygen exchange. Such circulatory dysfunction might participate in the multiple organ dysfunction that follows shock states.20 With normal saline administration, there is the added concern about hyperchloremic metabolic acidosis.18 Let us consider the not infrequent situation where a trauma patient is aggressively resuscitated with large volumes of crystalloids. After a while, despite being massively edematous with enough tissue edema to compromise organ function, such as pulmonary edema, the patient still has some evidence of being intravascularly depleted. In such a scenario, many physicians, especially in Europe or in an intensive care unit environment, would consider using colloid fluids for further resuscitation. Colloid fluids have many attractions and advantages over crystalloid resuscitation. They are more efficient than crystalloids in expanding plasma volume and achieve similar resuscitation endpoints faster and with much smaller volumes (Table 1).21 Regardless of the evidence that colloids also cause significant brain and lung edema,22,23 advocates of colloid use argue that by using smaller volumes and increasing the colloid-osmotic pressure, colloids reduce tissue edema compared with crystalloids. Colloids such as albumin also increase oxygen delivery significantly more than LR solution and improve organ microcirculation.24 26 The expansion in plasma volume and improvement in organ perfusion by albumin administration has been proposed as the explanation for the fact that albumin reduces renal failure and death in cirrhotic patients with spontaneous bacterial peritonitis.27 Even though the higher costs of colloids are frequently mentioned as a concern, these figures do not take into account the costs incurred as the Volume 54 Number 5

The Journal of TRAUMA Injury, Infection, and Critical Care

Table 2 Main Characteristics of the Four Types of Colloid Fluids

Source Albumin Human Commercial 5% 25% Increase Plasma Volume 0.71.3 None 4.05.0 Anticoagulation Half-Life 16 h Anaphylaxis (%) 0.51.5 Disadvantages Human product Risk infection Short supply Decrease serum calcium Implicate in ARF Accumulate SRE Maximum dose 20 mL/kg Interfere with serum glucose measure Modest effectiveness


Glucose polymers produced by bacteria

40-kDa 10% solution 70-kDa 6% solution

1.01.5 Von Willebrand-like syndrome 0.8 Increase bleeding time Increase fibrinolysis DVT/PE prophylaxis

612 h



Polydisperse peptides from bovine collagen Modified Polygelins

Broad range


Minimal (?)

3 h


Hetastarch Polymers of glucose (starch) derived from amylopectin

Varies with: Molecular weight Degree substitution C2/C6 ratio 6% hetastarch 10% pentastarch 1.5 1.01.3

Small effect

10 hdays


Adverse effect on renal transplant Increase amylase Affect white cell chemotaxis Maximum dose 1.5 L/ day

DVT, deep vein thrombosis; PE, pulmonary emboli; ARF, acute renal failure.

side effects, have a long shelf life, and are less expensive than albumin. With so many favorable characteristics, the next question is why colloids are not used more often. The answer is the evidence suggesting that the use of colloids may be associated with increased mortality. The next section of this review focuses on reviewing the meta-analyses on the controversy of choosing between colloids and crystalloids for resuscitation.

Velanovich (1989) and Bisonni et al. (1991)

Velanovich1 and Bisonni et al.2 were the first two metaanalyses ever performed on fluid resuscitation. These studies share many similarities. Meta-analysis had been described just a few years earlier, and Velanovich spent most of the Material and Methods section explaining the mathematical basis of the new methodology. Bisonni et al. criticized Velanovich for including one study with 472 patients whereas the remaining studies combined included only 354 patients, clearly impacting on the final analysis. Thus, Bisonni et al. simply repeated the earlier analysis, this time excluding the large study. In both analyses, the authors do not report how the primary randomized controlled trials (RCT) were collected or assessed for validity. Only trials with random allocation and that reported mortality rates were included. There are brief comments about nine RCTs that were excluded from Velanovichs analysis but not much elaboration about how data were extracted. There is no information about the different types of colloid or crystalloid fluids used, the different protocols, surgical interventions, age groups, or other patient characteristics. Eight RCTs were included in Velanovichs study, with 826 patients. With the exclusion of one study, Bisonni et al. analyzed 354 patients. Five studies included trauma patients. In Velanovichs meta-analysis, the use of colloids was assoMay Supplement 2003


Meta-analyses or systematic reviews were created to bring together information from randomized controlled trials of the same intervention. Meta-analyses have become a major source of information for clinicians and often provide the most accurate and authoritative guidelines to therapy. In reviewing the current literature on colloid versus crystalloid fluid resuscitation in critically ill patients, including trauma, the author encountered nine original meta-analyses1 8,11 and two updates of previous metaanalyses.9,10 Of the original meta-analyses, two studies by Wade et al. and another by Bunn et al. focused primarily on the effect of hypertonic saline resuscitation rather than on the debate between crystalloids and colloids.3,4,11 The two updates and the three meta-analyses on hypertonic saline were not included in this review, which focused on the remaining six reviews, as follows. S84

Crystalloids and Colloids in Trauma Resuscitation

ciated with an overall increase in mortality of 5.7% (95% confidence interval [CI], 9.4 20.8%). When trauma trials were analyzed separately, there was an increase in mortality of 12.3% (95% CI, 4.6 29.2%) associated with the use of colloid fluids. Using a much smaller group of patients, Bisonni et al. reported no statistically significant difference in overall mortality between colloids and crystalloids. They found, however, a clear trend toward increased mortality in hypovolemic patients (mostly trauma patients), where the mortality rate associated with colloids was 17.8% versus 7.3% for crystalloids. The results of these two studies are mostly of historical interest because of the limitations of the methodology used. For instance, in the 1989 analysis, the author was the only one responsible for searching for the studies, collecting the data, and performing the statistical analysis. To avoid bias, it is strongly recommended that more than one investigator carry out these tasks independently and then stipulate a manner for resolving the differences in interpretation. This and other methodologic flaws make the results of these early studies unreliable. The subsequent two meta-analyses were published in 1998, just months apart from each other.6,33 Both studies were performed in England, were published in the British Medical Journal, and reported very similar results. These two systematic reviews made front page in many newspapers and had a major impact on British physicians practice, with the use of albumin solutions in the United Kingdom decreasing by at least 40% by the end of that same year.34 increase in the absolute risk of dying of 4% (0 8%). The authors recommendation is that colloids should not be used outside RCTs. The study suffers from the same limitations as most meta-analyses included in this review, including low mortality rate (4.7%), inclusion of studies with insufficient information on interventions and patient characteristics, and a multitude of different resuscitation regimens. The inclusion of hypertonic saline is also a confounding factor. Hypertonic saline is often administered in conjunction with a colloid (most often with dextrans), making it difficult to classify as crystalloid or colloid. Still, their results cannot be ignored.

Cochrane Injuries Group Albumin Reviewers (1998)

The stated goal of the study by the Cochrane Injuries Group Albumin Reviewers6 was to quantify the effect on mortality of administering human albumin or plasma protein fraction for the resuscitation of critically ill patients. Like the previous study, methodology is clearly described and meets high standards. RCTs were identified by meticulous search including manual searching, reviewing meeting proceedings, and directly contacting authors. There was neither language restriction nor exclusion of unpublished studies. Allocation concealment was the main measurement of trial quality, and two reviewers independently extracted the data. Studies were separated into three categories: hypovolemia (caused by surgery or trauma), burns, and hypoalbuminemia. Data analysis and statistical methods are clearly described and included the funnel plot asymmetry test for published bias. Thirty studies met the inclusion criteria, comprising 1,419 patients and 156 deaths. The pooled RR of death with albumin or plasma protein fraction administration was 1.68 (95% CI, 1.26 2.23). For hypovolemic patients (surgery or trauma), the RR of death was 1.46 (95% CI, 0.972.22). The pooled difference in the risk of death with albumin was 6%, or 6 additional deaths for 100 patients resuscitated with albumin. The major criticisms of this study related not to the analysis itself but to the limitations of the primary studies, including the fact that it reviews 30 relatively small RCTs. However, in this analysis, the overall risk of death reached statistical significance and its results are consistent with the previous three meta-analyses.

Schierhout and Roberts (1998)

The study by Schierhout and Roberts33 was designed to measure the impact of resuscitation with any colloid (natural and synthetic) versus crystalloids in critically ill patients. The methodology used is clearly superior to that of the earlier studies. Inclusion criteria required random or quasi-random allocation and excluded neonates. Studies with hypertonic saline were included. Trial identification was comprehensive and included some manual searching in addition to direct contact with authors. Two reviewers independently collected data and determined eligibility. The studies were categorized into trauma, surgery, burns, and others and analyzed separately. The statistical methods included the funnel plot asymmetry analysis to identify publication or other selection bias. The mathematical analysis is clearly stated and is reproducible. Of the 48 RCTs identified, 37 were included. The conclusions, however, were based solely on the 19 studies (including 1,315 patients) that reported mortality rates. The pooled relative risk (RR) of death in all categories combined was 1.19 (95% CI, 0.98 1.45). For the trauma studies, the RR was 1.30 (95% CI, 0.951.77). These numbers did not reach statistical significance. However, taking into account that the risk of death in patients given colloids was 24% versus 20% with crystalloids, resuscitation with colloids resulted in an Volume 54 Number 5

Choi et al. (1999)

The objective of the study by Choi et al.7 was to systematically review the effects of isotonic crystalloids compared with colloids in fluid resuscitation of adult critically ill patients. Search criteria and study selection were very similar to the two meta-analyses published 1 year earlier. Choi et al. differed from those studies in that they excluded the studies with hypertonic saline, and instead of using allocation concealment as the main measurement of trial quality, they evaluated the rigor of several methodologic features such as randomization, consecutive patient selection, blinding, and S85

The Journal of TRAUMA Injury, Infection, and Critical Care

documentation of co-interventions. They also explored the relation between study quality and study results and measured the effects on mortality and endpoints such as pulmonary edema. Most importantly, they planned a priori a separate analysis of trauma patients. Their results showed no overall difference in mortality, pulmonary edema, or length of stay between crystalloid and colloid fluid resuscitation, but simply showed a trend toward lower mortality in favor of crystalloids. The authors themselves point to the limitations of such a study and comment that small but still clinically important differences may exist that were not detected. When the trauma subgroup was analyzed, however, the results demonstrated a statistically significant increase in mortality associated with the use of colloids. In reflecting over these findings, Choi et al. suggested that the results of this meta-analysis are best viewed as hypothesis generating rather than as a justification to ban the use of colloids.

Table 3 Most Frequently Mentioned Limitations of the Primary RCTs Included in the Meta-analyses Reviewed
Few studies were blinded No specific criteria for the diagnosis of different conditions Heterogenous: Indications for fluid resuscitation Interventions or resuscitation protocols Types of fluids used Subsets of patients (trauma and surgical hypovolemia analyzed together) Co-interventions Comorbidity Outdated protocols (50% studies performed before 1990) End point was not mortality Small number of patients included Small number of deaths Publication bias (preference for positive studies) Crossover

Wilkes and Navickis (2001)

The study by Wilkes and Navickis8 is the most recent and comprehensive of the meta-analyses performed on this subject. Wilkes and Navickis meta-analysis focuses on the use of albumin versus crystalloids in critically ill patients. Their stated goal is to test the hypothesis that albumin administration is not associated with increased mortality. To this end, they use rigorous and commendable methodology. They used a very comprehensive search strategy to minimize chance of publication and English-language bias. Article selection was explicit, with no restriction on clinical indications. Both authors extracted data independently, and there was a deliberate effort to avoid the inclusion of repeated data resulting from multiple reporting of the same studies. They assessed the quality of the primary studies according to blinding, allocation concealment, mortality as an endpoint, and crossover. A table disclosing the attributes of each study is also presented. Of the 415 studies on this subject, 55 met the study requirements, including 3,504 randomly assigned patients with 525 deaths, making it the analysis with the largest number of studies and patients to date. Twenty-seven RCTs were performed on surgical or trauma resuscitation, involving 1,504 patients. Other RCTs focused on burns, hypoalbuminemia, high-risk neonates, ascites, acute respiratory distress syndrome, hyperbilirubinemia, septic and hypovolemic shock, ischemic stroke, vascular leaky syndrome, and ovarian hyperstimulation syndrome. Their pooled relative risk of death was 1.11 (95% CI, 0.951.28) for all patients and 1.12 (95% CI, 0.851.46) for surgery and trauma patients. The conclusion of the authors is that there is no evidence that albumin significantly affects mortality across all trials and for the subgroup of surgery and trauma patients. Furthermore, the higher the methodologic quality of the studies included (blinding, mortality as an endpoint, no crossover, and 100 or more patients), the lower the estimated relative risk, thus S86

favoring albumin. Their conclusion is that the results of this study should allay concerns about the safety of albumin. Although data extraction and synthesis were excellently performed, the conclusions are intriguing, especially when compared with previous meta-analyses.6,33 As pointed out in the accompanying editorial comment by Cook and Guyatt,35 the results of this study are similar to the other meta-analyses but the interpretations clearly dissimilar. The editorial recognizes that the results of the meta-analysis by Wilkes and Navickis show no statistically significant increase in mortality; however, the point estimate indicates an increase in relative risk of death of more than 10% for surgical and trauma patients and a confidence interval consistent with a relative overall increase in mortality up to 46%. The editorials conclusion is that point estimates that suggest harm and confidence intervals that include important increases in mortality cannot allay concerns about the potentially harmful effects of albumin.35 The best evaluation of the results from this meta-analysis is that there is a trend toward increased mortality when albumin is used to resuscitate surgical and trauma patients, a trend that does not reach statistical significance.


It is interesting that Wilkes and Navickis reported in their study that they found 415 potentially relevant RCTs on albumin versus crystalloid resuscitation.8 This enormous amount of data on one specific topic explains the fact that meta-analyses are being used more frequently to set guidelines for medical practice.35 However, as is clear in the present review, meta-analyses need to be interpreted with caution and may not always provide the definitive, sound rationale for changing current practices.36 The first limitation of a meta-analysis is that it can only be as good as the quality of the individual RCTs it includes. Table 3 summarizes some of the weaknesses of the primary clinical trials on fluid resuscitation. The observation that May Supplement 2003

Crystalloids and Colloids in Trauma Resuscitation

approximately half of the studies were performed more than a decade ago might explain many of the methodologic shortcomings. Another important limitation of the primary RCTs is the lack of information on co-interventions such as blood transfusion and even surgery. Therefore, the first conclusion of the present review is that there is an urgent need for well-designed clinical trials on fluid resuscitation. However, the quality of the primary RCTs is not the only factor limiting the meta-analyses on fluid resuscitation. The meta-analyses reviewed also have methodologic deficiencies that have come to the surface in this review. Despite having similar goals, each meta-analysis identified a very different group of RCTs, whereas many large and well-designed RCTs were ignored by most meta-analyses.8 Webb pointed out that 20 of 30 RCTs (67%) involving colloid administration were included in one but not in the other colloid meta-analysis.36 The meta-analyses also included very heterogeneous populations for analysis. Even when only trauma was being considered, trauma and elective surgical patients were often pooled and analyzed as one group.8 Another limitation is the striking fact that similar mathematical results can be interpreted so differently. As pointed out by Cook and Guyatt, the results of the effect of albumin on mortality were interpreted as alarming in one study, with the author urging to restrict its use, whereas similar results in another study were interpreted as reassuring of the safety of albumin.35 This leads to the second conclusion of this overview, that meta-analysis should be interpreted cautiously and, as suggested by Choi et al. in relation to fluid resuscitation, viewed as hypothesis generating given the limitations in both study design and limitations of the primary RCTs.7 Finally, all six meta-analyses examined in this overview demonstrated a trend toward increased mortality when colloids were used to resuscitate trauma patients. In fact, the meta-analysis that was designed a priori to investigate the effect of crystalloids and colloids in trauma resuscitation was the only one showing a statistical difference in mortality in favor of crystalloids.7 Therefore, even when all limitations and nuances of interpretation are considered, one piece of evidence that comes out is that trauma patients should probably continue to be resuscitated with crystalloids.
5. Schierhout G, Roberts I. Fluid resuscitation with colloid or crystalloid solutions in critically ill patients: a systematic review of randomised trials. BMJ. 1998;316:961964. Human albumin administration in critically ill patients: systematic review of randomised controlled trials. Cochrane Injuries Group Albumin Reviewers. BMJ. 1998;317:235240. Choi PT, Yip G, Quinonez LG, Cook DJ. Crystalloids vs. colloids in fluid resuscitation: a systematic review. Crit Care Med. 1999; 27:200 210. Wilkes MM, Navickis RJ. Patient survival after human albumin administration: a meta-analysis of randomized, controlled trials. Ann Intern Med. 2001;135:149 164. Alderson P, Schierhout G, Roberts I, Bunn F. Colloids versus crystalloids for fluid resuscitation in critically ill patients. Cochrane Database Syst Rev. 2000;2:CD000567. Bunn F, Lefebvre C, Li WP, Li L, Roberts I, Schierhout G. Human albumin solution for resuscitation and volume expansion in critically ill patients: the Albumin Reviewers. Cochrane Database Syst Rev. 2000;2:CD001208. Bunn F, Roberts I, Tasker R, Akpa E. Hypertonic versus isotonic crystalloid for fluid resuscitation in critically ill patients. Cochrane Database Syst Rev. 2000;4:CD002045. Fakhry SM, Alexander J, Smith D, Meyer AA, Peterson HD. Regional and institutional variation in burn care. J Burn Care Rehabil. 1995;16:86 90. Needham DM, Detsky AS, Stewart TE. Recent evidence for intravenous fluid choice in patients with severe infection. Intensive Care Med. 2001;27:609 612. Annane D, Bellissant E. Prognostic value of cortisol response in septic shock. JAMA. 2000;284:308 309. Rizoli SB, Rotstein OD, Sibbald WJ. The immunological effects of hypertonic saline. In: Vincent JL, ed. 2002 Yearbook of Intensive Care and Emergency Medicine. Berlin: Springer-Verlag; 2002:446 453. Rizoli SB, Kapus A, Fan J, Li YH, Marshall JC, Rotstein OD. Immunomodulatory effects of hypertonic resuscitation on the development of lung inflammation following hemorrhagic shock. J Immunol. 1998;161:6288 6296. American College of Surgeons, Committee on Trauma. In: Advanced Trauma Life Support Manual. Chicago: American College of Surgeons; 1997:21 60. Orlinsky M, Shoemaker W, Reis ED, Kerstein MD. Current controversies in shock and resuscitation. Surg Clin North Am. 2001; 81:12171262. Doyle JA, Davis DP, Hoyt DB. The use of hypertonic saline in the treatment of traumatic brain injury. J Trauma. 2001;50:367383. Mazzoni MC, Borgstrom P, Intaglietta M, Arfors KE. Capillary narrowing in hemorrhagic shock is rectified by hyperosmotic salinedextran reinfusion. Circ Shock. 1990;31:407 418. Tremblay LN, Rizoli SB, Brenneman FD. Advances in fluid resuscitation of hemorrhagic shock. Can J Surg. 2001;44:172179. Ernest D, Belzberg AS, Dodek PM. Distribution of normal saline and 5% albumin infusions in septic patients. Crit Care Med. 1999; 27:46 50. Lucas CE, Ledgerwood AM, Higgins RF, Weaver DW. Impaired pulmonary function after albumin resuscitation from shock. J Trauma. 1980;20:446 451. Lang K, Boldt J, Suttner S, Haisch G. Colloids versus crystalloids and tissue oxygen tension in patients undergoing major abdominal surgery. Anesth Analg. 2001;93:405 409. Groeneveld AB. Albumin and artificial colloids in fluid management: where does the clinical evidence of their utility stand? Crit Care. 2000;4(suppl 2):S16 S20. Vincent JL. Issues in contemporary fluid management. Crit Care. 2000;4(suppl 2):S1S2.









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1. Velanovich V. Crystalloid versus colloid fluid resuscitation: a metaanalysis of mortality. Surgery. 1989;105:6571. 2. Bisonni RS, Holtgrave DR, Lawler F, Marley DS. Colloids versus crystalloids in fluid resuscitation: an analysis of randomized controlled trials. J Fam Pract. 1991;32:387390. 3. Wade CE, Kramer GC, Grady JJ, Fabian TC, Younes RN. Efficacy of hypertonic 7.5% saline and 6% dextran-70 in treating trauma: a meta-analysis of controlled clinical studies. Surgery. 1997;122:609 616. 4. Wade CE, Grady JJ, Kramer GC, Younes RN, Gehlsen K, Holcroft JW. Individual patient cohort analysis of the efficacy of hypertonic saline/dextran in patients with traumatic brain injury and hypotension. J Trauma. 1997;42:S61S65.






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27. Sort P, Navasa M, Arroyo V, et al. Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. N Engl J Med. 1999;341:403 409. Vincent JL. Fluid management: the pharmacoeconomic dimension. Crit Care. 2000;4(suppl 2):S33S35. Yim JM, Vermeulen LC, Erstad BL, Matuszewski KA, Burnett DA, Vlasses PH. Albumin and nonprotein colloid solution use in US academic health centers. Arch Intern Med. 1995;155:2450 2455. de Jong E, Levi M. Effects of different plasma substitutes on blood coagulation: a comparative review. Crit Care Med. 2001;29:12611267. Treib J, Baron JF, Grauer MT, Strauss RG. An international view of hydroxyethyl starches. Intensive Care Med. 1999;25:258 268. Treib J, Haass A, Pindur G, Grauer MT, Wenzel E, Schimrigk K. All medium starches are not the same: influence of the degree of hydroxyethyl substitution of hydroxyethyl starch on plasma volume, hemorrheologic conditions, and coagulation. Transfusion. 1996; 36:450 455. 33. Schierhout G, Roberts I. Fluid resuscitation with colloid or crystalloid solutions in critically ill patients: a systematic review of randomised trials. BMJ. 1998;316:961964. 34. Roberts I, Edwards P, McLelland B. More on albumin: use of human albumin in UK fell substantially when systematic review was published. BMJ. 1999;318:1214 1215. 35. Cook D, Guyatt G. Colloid use for fluid resuscitation: evidence and spin. Ann Intern Med. 2001;135:205208. 36. Webb AR. The appropriate role of colloids in managing fluid imbalance: a critical review of recent meta-analytic findings. Crit Care. 2000;4(suppl 2):S26 S32.

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