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technical considerations involved with RRT, including the dose and type of RRT support, issues not directly studied in the report by Modem et al (8), are controversial and can only be thoroughly vetted by larger multicenter RCTs. Since the publication of several PP-CRRT articles, the awareness of fluid overload as a clinical “symptom” with negative consequence has prompted more diligence to fluid removal and prevention of fluid overload states. For this reason, it has become increasingly important to identify RRT initiation triggers associated with poor outcome that are not fluid related. Reports such as this one, particularly in pediatrics, underscore the importance of considering early initiation of RRT. The future of RRT epidemiologic study will include RCTs involving AKI biomarker–based decision algorithms to detect and accurately predict RRT need. Clinical trials based on renal angina context–based AKI stratification (12) and plasma levels of novel biomarkers such as neutrophil gelatinase–associated lipocalin (13) may offer the possibility of identifying initiation triggers independent of disease severity and kidney dysfunction, allowing more pure association with outcomes.

REFERENCES

1. Clark E, Wald R, Walsh M, et al; Canadian Acute Kidney Injury (CANAKI) Investigators: Timing of initiation of renal replacement therapy for acute kidney injury: A survey of nephrologists and intensivists in Canada. Nephrol Dial Transplant 2012; 27:2761–2767 2. Bagshaw SM, Wald R, Barton J, et al: Clinical factors associated with initiation of renal replacement therapy in critically ill patients with acute kidney injury—A prospective multicenter observational study. J Crit Care 2012; 27:268–275

3. Basu RK, Wheeler DS, Goldstein S, et al: Acute renal replacement therapy in pediatrics. Int J Nephrol 2011; 2011:785392 4. Goldstein SL: Advances in pediatric renal replacement therapy for acute kidney injury. Semin Dial 2011; 24:187–191 5. Group KW: Kidney disease improving global outcomes; clinical practice guideline for acute kidney injury. Kidney Int Suppl 2012; 2:19–33 6. Goldstein SL, Currier H, Graf CD, et al: Outcome in children receiving continuous venovenous hemofiltration. Pediatrics 2001; 107:1309–1312 7. Sutherland SM, Zappitelli M, Alexander SR, et al: Fluid overload and mortality in children receiving continuous renal replacement therapy: The prospective pediatric continuous renal replacement therapy registry. Am J Kidney Dis 2010; 55:316–325 8. Modem V, Thompson M, Gollhoger D, et al: Timing of Continuous Renal Replacement Therapy and Mortality in Critically Ill Children. Crit Care Med 2014; 42:943–953 9. Shiao CC, Wu VC, Li WY, et al; National Taiwan University Surgical Intensive Care Unit-Associated Renal Failure Study Group: Late initiation of renal replacement therapy is associated with worse outcomes in acute kidney injury after major abdominal surgery. Crit Care 2009; 13:R171 10. Liu KD, Himmelfarb J, Paganini E, et al: Timing of initiation of dialysis in critically ill patients with acute kidney injury. Clin J Am Soc Nephrol 2006; 1:915–919 11. Bouman CS, Oudemans-Van Straaten HM, Tijssen JG, et al: Effects of early high-volume continuous venovenous hemofiltration on survival and recovery of renal function in intensive care patients with acute renal failure: A prospective, randomized trial. Crit Care Med 2002; 30:2205–2211 12. Basu RK, Zappitelli M, Brunner L, et al: Derivation and validation of the renal angina index to improve the prediction of acute kidney injury in critically ill children. Kidney Int 2013 Sep 18. [Epub ahead of print] 13. Cruz DN, de Cal M, Garzotto F, et al: Plasma neutrophil gelatinaseassociated lipocalin is an early biomarker for acute kidney injury in an adult ICU population. Intensive Care Med 2010; 36:444–451

Fluid Resuscitation: Less Is More* David Dries, MSE, MD HealthPartners Medical Group Regions Hospital St. Paul, MN; and Professor of Surgery and Anesthesiology University of Minnesota Minneapolis, MN

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s Dutton (1) points out in a recent review, no therapy in trauma comes without risk. Although tourniquets and pressure dressings may stop bleeding, they increase local tissue injury. Aggressive airway management includes risks of inability to intubate, compromise of tenuous hemodynamics,

*See also p. 954. Key Words: blood; crystalloids; prehospital; resuscitation; trauma The author has disclosed that he does not have any potential conflicts of interest. Copyright © 2013 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins DOI: 10.1097/CCM.0000000000000171

Critical Care Medicine

and subtle dangers such as hyperventilation with reduced cerebral blood flow. Most resuscitative fluids are given at room temperature, and if given rapidly or in large amounts, the negative thermal load may produce a significant metabolic strain. Hypothermia may develop and a cascade of physiological distortion deepens. For example, the primary rate constant for individual clotting reactions is decreased by hypothermia, and synchronization of the clotting cascade is disrupted. Other metabolic issues include hyperchloremic metabolic acidosis associated with administration of saline solutions, renal dysfunction with chloride loading, increased lactate levels, hypotonicity, and cardiotoxicity, particularly with additives such as lactate and acetate (1, 2). Bulk administration of IV fluid produces important mechanical effects on the circulation. In a vasoconstricted patient after injury, as little as 100 mL of fluid may increase end-diastolic pressure sufficiently to raise cardiac output and blood pressure. Increased intravascular pressure may improve perfusion in nonconstricted vascular beds but may also reverse hemostatic reflexes and exert pressure on extravascular clot. Fluid administration leading to increased blood pressure in the setting of uncontrolled hemorrhage predicts rebleeding (1, 3, 4). The recently completed www.ccmjournal.org

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Editorials

Fluid Expansion As Supportive Therapy study comparing boluses of albumin or saline with no boluses during resuscitation of over 3,000 febrile children demonstrated a significant increase in the rate of death at 48 hours after initiation of bolus resuscitation whether albumin or saline was used for this therapy. The principal cause of death in these children was cardiovascular collapse rather than fluid overload or neurologic causes. Bleeding was not involved. An adverse interaction between bolus fluid administration and compensatory neurohumeral responses was suggested. Thus, even the traditional fluid bolus may be deleterious (5, 6). Administration of IV products other than blood components will change the composition of circulating blood with consequences measured in coagulopathy, disruption of endothelium, loss of membrane integrity, and extracellular edema. Resuscitation is required but how best to accomplish it remains unclear. An old adage in shock management is to replace what the patient has lost. If blood is lost, then blood should be replaced. The dehydrated patient is a good candidate for crystalloids. Aggressive administration of crystalloids to the bleeding patient may create acute respiratory distress syndrome and hepatic and renal failure (4, 5, 7). Despite a lack of evidence demonstrating clear benefit to prehospital fluid resuscitation, this practice is considered to be standard of care (1, 3, 7). Although we do not have guidance about the good, bad, and optimal, national prehospital care guidelines are shifting to recognize the limitations of uncontrolled early fluid administration. The Advanced Trauma Life Support course of the “American College of Surgeons” describes “balanced resuscitation” with delayed aggressive fluid administration, even if lower than normal blood pressure is accepted, until definitive surgical control of bleeding is possible. If fluids are given, how much is appropriate? Even with restoration of normal blood pressure, heart rate, and urine output, up to 85% of severely injured trauma victims will have evidence of inadequate tissue oxygenation reflected in metabolic acidosis or evidence of gastric mucosal ischemia. Unfortunately, metabolic variables and oxygen transport data are not readily available to field personnel (8, 9). Within the body of evidence favoring restricted fluid administration in the initial management of injury, significant ambiguity exists. Wang et al (10) capture the limitations of available work in this issue of Critical Care Medicine. After discussion of available evidence in a meta-analysis, limitations of available studies are revealed. Much of the basic work in resuscitation of uncontrolled hemorrhage has been conducted in animals as clinical studies pose multiple, logistical, and ethical difficulties. Wang et al (10) found only four applicable, randomized controlled trials between 1994 and 2011. Characteristics of patients including the proportion of blunt and penetrating trauma varied. Many trials excluded traumatic brain injury, a key determinant of outcome. The location of resuscitation differed among included trials and the proportion of men participating ranged from 64% to 94%. Blood pressure targets, a poor indication of perfusion, were most commonly employed to identify patients for resuscitation. These authors identified only seven relevant observational studies between the years 1990 and 2012. Again, the largest portion of subjects was male. In contrast to the randomized controlled trials, 1006

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observational studies more frequently included patients with blunt trauma and traumatic brain injury. Burned patients were not specifically excluded, although burn resuscitation includes unique considerations (11). The majority of the studies, but not all studies, were performed in the prehospital setting. Other issues include inconsistent reporting of mortality and time to definitive care. Exsanguination was the most common scenario for mortality in these trials. Our inability to study a process which is virtually impossible to blind is easy to recognize. This meta-analysis can be recommended for careful assembly of data on which subsequent trials may be fashioned and review of limitations in present work. The future may be reflected in a recent article from the “Pacific Coast Surgical Association.” A single trauma center studied 174 trauma patients who ultimately required massive transfusion (> 10 units of RBCs in 24 hr) or the institutional massive transfusion protocol. In this review of practice conducted over a 6-year interval, crystalloid infusion over the first 24 hours after injury and the total number of blood products given decreased significantly. Injury severity and mortality remained stable. A shift toward reduced crystalloid volume and reconstitution of whole blood from component products was identified. Clearly, we need more data for optimal use of both salt solutions and blood products in the early management of injury. For the present, I believe we can safely say that “less is more” (12, 13).

REFERENCES

1. Dutton RP: Resuscitative strategies to maintain homeostasis during damage control surgery. Br J Surg 2012; 99(Suppl 1):21–28 2. Yunos NM, Bellomo R, Hegarty C, et al: Association between a chlorideliberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults. JAMA 2012; 308:1566–1572 3. Krausz MM: Initial resuscitation of hemorrhagic shock. World J Emerg Surg 2006; 1:14 4. McSwain NE, Champion HR, Fabian TC, et al: State of the art of fluid resuscitation 2010: Prehospital and immediate transition to the hospital. J Trauma 2011; 70(Suppl):S2–S10 5. Myburgh JA, Mythen MG: Resuscitation fluids. N Engl J Med 2013; 369:1243–1251 6. Maitland K, Kiguli S, Opoka RO, et al; FEAST Trial Group: Mortality after fluid bolus in African children with severe infection. N Engl J Med 2011; 364:2483–2495 7. Cotton BA, Jerome R, Collier BR, et al; Eastern Association for the Surgery of Trauma Practice Parameter Workgroup for Prehospital Fluid Resuscitation: Guidelines for prehospital fluid resuscitation in the injured patient. J Trauma 2009; 67:389–402 8. Tisherman SA, Barie P, Bokhari F, et al: Clinical practice guideline: Endpoints of resuscitation. J Trauma 2004; 57:898–912 9. American College of Surgeons Committee on Trauma: Advanced Trauma Life Support—ATLS, Ninth Edition. Chicago, IL: American College of Surgeons, 2012 10. Wang C-H, Hsieh W-H, Chou H-C, et al: Liberal Versus Restricted Fluid Resuscitation Strategies in Trauma Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials and Observational Studies. Crit Care Med 2014; 42:954–961 11. Endorf FW, Dries DJ: Burn resuscitation. Scand J Trauma Resusc Emerg Med 2011; 19:69 12. Kutcher ME, Kornblith LZ, Narayan R, et al: A paradigm shift in trauma resuscitation: Evaluation of evolving massive transfusion practices. JAMA Surg 2013; 148:834–840 13. Dries DJ: The contemporary role of blood products and components used in trauma resuscitation. Scand J Trauma Resusc Emerg Med 2010; 18:63 April 2014 • Volume 42 • Number 4