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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.
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. rizoli@sw.ca. DOI: 10.1097/01.TA.0000064525.03761.0C
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D5W lactated Ringers 7.5% hypertonic saline 5% albumin 25% albumin Pentastarch
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
Dextran
1.01.5 Von Willebrand-like syndrome 0.8 Increase bleeding time Increase fibrinolysis DVT/PE prophylaxis
612 h
1.53
Gelatin
Broad range
1.0
Minimal (?)
3 h
0.0510
Varies with: Molecular weight Degree substitution C2/C6 ratio 6% hetastarch 10% pentastarch 1.5 1.01.3
Small effect
10 hdays
0.1
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.
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
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.
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REFERENCES
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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