WTA 2014 PLENARY PAPER

Crystalloid administration during trauma resuscitation: Does less really equal more? John P. Sharpe, MD, Louis J. Magnotti, MD, Martin A. Croce, MD, Elena M. Paulus, MD, Thomas J. Schroeppel, MD, Timothy C. Fabian, MD, and Jordan A. Weinberg, MD Current direction in trauma resuscitation includes emphasis on minimizing crystalloid, along with early transfusion of blood products. Although evidence suggests that higher crystalloid volume during the first 24 hours is associated with negative outcomes, the effect of crystalloid administration during initial resuscitation remains unclear. The purpose of this study was to evaluate the impact of the ratio of crystalloid to packed red blood cells (C/PRBCs) infused during initial emergency department resuscitation on pulmonary morbidity and mortality. METHODS: Over 6.5 years at a Level 1 trauma center, prospective data were collected on patients that received more than 1 PRBC unit in the resuscitation room. C/PRBC was defined as the ratio of crystalloid infused in liters to the units of PRBCs transfused in the resuscitation room. Patients were stratified by high ratio (90.75) versus low ratio (G0.75). Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were determined for the association between C/PRBC group and outcomes, namely, adult respiratory distress syndrome (ARDS), 24-hour mortality, and in-hospital mortality. RESULTS: A total of 383 patients met study criteria: 192 (50%) in the high-ratio and 191 (50%) in the low-ratio group. Variables associated with in-hospital mortality were Injury Severity Score (ISS) (OR, 1.05; 95% CI, 1.03Y1.07), admission base excess (OR, 0.94; 95% CI, 0.90Y0.98), and time in the resuscitation room (OR, 1.01; 95% CI, 1.00Y1.03). Variables associated with 24-hour mortality were ISS (OR, 1.04; 95% CI, 1.02Y1.06) and base excess (OR, 0.95; 95% CI, 0.91Y1.00). Only ISS (OR, 1.05; 95% CI, 1.02Y1.07) was associated with ARDS. ARDS (OR, 1.43; 95% CI, 0.75Y2.73), 24-hour mortality (OR, 0.89; 95% CI, 0.49Y1.63), and in-hospital mortality (OR, 0.89; 95% CI, 0.52Y1.53) were not associated with C/PRBC. CONCLUSION: In this cohort of patients receiving PRBC in the resuscitation room, factors related primarily to injury severity were associated with pulmonary morbidity and mortality, but C/PRBC was not. Pertaining to initial resuscitation, the purported benefit of crystalloid limitation was not observed. (J Trauma Acute Care Surg. 2014;77: 828Y832. Copyright * 2014 by Lippincott Williams & Wilkins) LEVEL OF EVIDENCE: Therapeutic study, level IV; prognostic study, level III. KEY WORDS: Transfusion; resuscitation; crystalloid. BACKGROUND:

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emorrhagic shock research performed by Shires1 in the 1960s helped establish the principle of the extracellular fluid deficit, and the practice of resuscitating with balanced salt solution in addition to blood transfusion was born. In experiments with splenectomized dogs, the compensatory redistribution of extracellular fluid that occurs following hemorrhage was demonstrated, and a significant survival advantage associated with the administration of intravenous crystalloid solution in addition to the reinfusion of shed blood was also observed. Initial resuscitation of the trauma patient with an intravenous bolus of crystalloid subsequently became a tenet of trauma resuscitation, formally incorporated into the guidelines of the Advanced Trauma Life Support course of the American College of Surgeons.2

Submitted: January 15, 2014, Revised: June 15, 2014, Accepted: June 25, 2014, Published online: September 22, 2014. From the Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee. This study was presented at the 44th Annual Meeting of the Western Trauma Association, March 2Y7, 2014, in Steamboat Springs, Colorado. Address for reprints: Jordan A. Weinberg, MD, Department of Surgery, University of Tennessee Health Science Center, 901 Madison Ave, #224, Memphis, TN 38163; email: [email protected]. DOI: 10.1097/TA.0000000000000424

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Concern, however, over the use of crystalloid solutions in the trauma setting has developed in recent years. Large-volume crystalloid resuscitation has been implicated in the development of cardiac, pulmonary, and coagulopathic complications.3,4 With respect to initial resuscitation, some advocate that the liberal administration of crystalloid to a patient in hemorrhagic shock worsens the shock state by ‘‘popping the clot’’ and contributing to ongoing bleeding.5,6 More recently, the concept of hemostatic resuscitation for severe bleeding has been emphasized, whereby blood components are administered in a balanced fashion to approximate whole-blood transfusion (a 1:1:1 ratio of red blood cells, plasma, and platelets), and the administration of potentially harmful crystalloid is minimized.7,8 While much of the recent trauma resuscitation literature has focused on the comparative evaluation of different ratios of plasma and platelets to red blood cells administered during massive transfusion, the relative role of crystalloid versus blood transfusion has yet to be well characterized. To address this issue, Neal et al.9 proposed the crystalloidYtoYpacked red blood cell ratio (C/PRBC). In their study, they identified that a cumulative ratio of greater than 1.5:1 (calculated at 24 hours following admission) was independently associated with a higher risk of multiple-organ failure, adult respiratory distress syndrome (ARDS), and abdominal compartment syndrome. It is notable, however, that these observations concern fluid and J Trauma Acute Care Surg Volume 77, Number 6

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blood administration over 24 hours. The effect of crystalloid administration during initial resuscitation of the trauma patient remains unclear. The purpose of this study was to evaluate the impact of C/PRBC in the resuscitation room of a Level 1 trauma center on patient outcomes.

PATIENTS AND METHODS Approval for this study was granted by the University of Tennessee Health Science Center Institutional Review Board. Since 2006, information regarding every patient who requires trauma activation at the Presley Regional Trauma Center has been maintained in a prospective resuscitation registry. Data regarding the type and timing of fluid and blood product administration, laboratory results, physiologic parameters, and mortality outcomes are recorded. Patients who received at least one PRBC unit in the resuscitation room between March 2006 and August 2012 were identified from the resuscitation registry. Patient care in the resuscitation room was directed by the on-call attending trauma surgeon, and the decision to administer crystalloid, PRBCs, plasma, platelets, and/or hydroxyethyl starch solution was at the discretion of the surgeon. Patients that received hypertonic saline and those with missing values for fluid administration were excluded from the analysis. Patients that arrived in extremis (no vitals signs on presentation) and/or died in the resuscitation room were also excluded from the analysis. Cumulative amounts of crystalloid and blood products were calculated for each patient in the resuscitation room. The C/PRBC was defined as the ratio of crystalloid infused in liters to the units of PRBCs transfused in the resuscitation room. Based on the median C/PRBC value for the study population, patients were divided into high-ratio (Q0.75) and low-ratio (G0.75) groups. Outcomes included 24-hour mortality, inhospital mortality, ventilator-free days, and PaO2/FIO2 (P/F) ratio (ratio of the arterial oxygen concentration to the fraction of inspired oxygen) at 48 hours of hospitalization. ARDS was defined as P/F ratio at 48 hours less than 200. Clinical characteristics and outcomes were then compared between those patients in the high-ratio and low-ratio groups. Continuous variables were compared using Student’s t test, and categorical variables were tested using X2 analysis or Fisher’s exact test where appropriate. Variables that had p G 0.2 on univariable analysis were chosen as prospective covariates. Stepwise multiple logistic regression analysis was then performed to determine variables significantly associated with 24-hour mortality, inhospital mortality, and ARDS. p G 0.05 was considered statistically significant.

RESULTS During the 6.5-year study period, 383 patients received one or more PRBC unit during initial resuscitation and were included in the study: 192 patients (50%) in the high-ratio group and 191 patients (50%) in the low-ratio group. The mean patient age was 41 years, and 67% were male. The incidence of blunt injuries was 63%, and the mean Injury Severity Score (ISS) was 29. Overall 24-hour mortality and in-hospital mortality were 19% (73 deaths) and 31% (119 deaths), respectively.

Clinical characteristics for the two groups are presented in Table 1. Patients in the high-ratio group were similar to those in the low-ratio group with respect to age, sex, mechanism of injury, admission systolic blood pressure, admission base excess, and Glasgow Coma Scale (GCS) score. However, patients in the high-ratio group had higher mean ISS (32 vs. 27, p e 0.001) and admission heart rate (118 vs. 112, p = 0.02) compared with those in the low-ratio group. In addition, patients in the high-ratio group spent more time in the resuscitation room (mean, 50 minutes vs. 40 minutes, p e 0.001). Patients in the high-ratio group received less PRBCs (mean, 2.7 U vs. 4.0 U, p = 0.001) and platelets (0.05 U vs. 0.70 U, p = 0.04) and more crystalloid (mean, 4.0 L vs. 1.3 L, p e 0.001) in the resuscitation room, compared with the low-ratio group. The volume of crystalloid administered in the high-ratio group ranged from 1.0 L to 11.6 L and ranged from 0.5 L to 8.2 L in the low-ratio group. Patients in the low-ratio group also had a higher incidence of resuscitation room administration of hydroxyethyl starch (34% vs. 18%, p e 0.001) Table 2 demonstrates clinical outcomes for the two groups. Patients in the low-ratio group were similar to those in the high-ratio group with respect to both P/F ratio at 48 hours (mean, 287 vs. 234, p = 0.12) and ventilator-free days (mean, 3.8 days vs. 3.4 days, p = 0.16). The low-ratio group was found to have a significantly lower incidence of ARDS (24% vs. 35%, p = 0.03). No difference was observed between the groups with respect to 24-hour mortality (17% vs. 21%, p = .38) or inhospital mortality (28% vs. 34%, p = 0.16). Based on the results of the univariable analysis, covariates for the regression model included mechanism of injury, ISS, admission heart rate, admission base excess, time in the resuscitation room, the use of hydroxyethyl starch during initial resuscitation, and resuscitation room platelet and plasma transfusions. The initial regression analyses are demonstrated in Table 3. After adjusting for these potential confounding variables, C/PRBC was not found to be significantly associated with ARDS (adjusted odds ratio [OR], 1.43; 95% confidence TABLE 1. Comparison of High-Ratio (C/PRBC Q 0.75) Group to Low-Ratio (C/PRBC G 0.75) Group

Age, y Male, % Blunt injury, % Admission systolic blood pressure Admission heart rate Admission GCS score ISS Admission base excess Minutes in the resuscitation room Hydroxyethyl starch, % Resuscitation room crystalloid, L Resuscitation room RBC, U Resuscitation room plasma, U Resuscitation room platelets, U

High Ratio (n = 192)

Low Ratio (n = 191)

p

41 67 73 107 118 10 32 j9.4 50 18 4.0 2.7 0.18 0.05

41 67 63 111 112 10.5 27 j8.1 40 34 1.3 4 0.34 0.70

0.94 0.88 0.09 0.27 0.02 0.34 G0.001 0.06 G0.001 G0.001 G0.001 0.001 0.10 0.04

Variables presented as means unless stated otherwise.

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TABLE 2. Comparison of Clinical Outcomes of High-Ratio (C/PRBC Q 0.75) Group to Low-Ratio (C/PRBC G 0.75) Group High Ratio (n = 192) Low Ratio (n = 191) P/F ratio at 48 h ARDS, % Ventilator-free days 24-h mortality, % In-hospital mortality, %

234 35 3.4 21 34

287 24 3.8 17 28

TABLE 4. Independent Predictors of ARDS, 24-Hour Mortality, and In-Hospital Mortality

p 0.12 0.03 0.51 0.38 0.16

Variables presented as means unless stated otherwise. P/F ratio is the ratio of the arterial oxygen concentration (PaO2) to the fraction of inspired oxygen (FIO2).

interval [CI], 0.75Y2.73), 24-hour mortality (adjusted OR, 0.89; 95% CI, 0.49Y1.63), or in-hospital mortality (adjusted OR, 0.89; 95% CI, 0.52Y1.53). Stepwise multiple logistic regression analysis identified ISS, admission base excess, and time in the resuscitation room as independent predictors of inhospital mortality and only ISS as an independent predictor of 24-hour mortality and of ARDS (Table 4).

DISCUSSION A 1-L to 2-L bolus of intravenous lactated Ringer’s solution has been recommended as the first-line therapy for the patient suspected to be in hemorrhagic shock since the 1960s, and it subsequently became a central component of the Advanced Trauma Life Support course.10 Although the importance of treating hemorrhage urgently with blood transfusion had never been in question, the rationale for initiating resuscitation with crystalloid was to initiate the replacement of extracellular fluid losses and, in addition, to provide a diagnostic/ therapeutic maneuver to determine the degree of preexisting or ongoing blood loss.1 Specifically, in patients with self-limited hemorrhage (such as resulting from a closed femur fracture), infusion of the balanced salt solution may be all that is needed to correct hemodynamic instability, avoiding exposure to allogeneic blood products. A transient or negligible response to intravenous crystalloid, however, suggests ongoing, uncontrolled bleeding, necessitating the urgent transfusion of blood products. Recently, however, concern over the use of crystalloid has developed among trauma surgeons. Postinjury complications, including respiratory distress syndrome and abdominal

ARDS

24-h Mortality

In-Hospital Mortality

ISS 1.06 (1.03Y1.08) 1.04 (1.02Y1.06) 1.05 (1.03Y1.07) Base excess V V 0.95 (0.91Y0.99) Minutes in the V V 1.01 (1.00Y1.02) resuscitation room Data presented as ORs with 95% CIs.

compartment syndrome, have been attributed to the liberal use of crystalloids.11Y13 The possible exacerbation of bleeding before hemorrhage control has prompted interest in hypotensive resuscitation.5,14 In addition, the recognition of early coagulopathy among trauma patients has led to the promotion of hemostatic resuscitation, whereby balanced transfusion of red blood cells, plasma, and platelets is performed to approximate fresh wholeblood transfusion in an effort to correct the early coagulopathy as well as to avoid its propagation by hemodilution.8,15,16 With hemostatic resuscitation, the role of crystalloid has been limited to that of carrier solution for blood products.6 The use of crystalloid during resuscitation and treatment of massive hemorrhage has been previously studied, both in secondary analyses of multi-institutional cohorts and retrospective single-institution studies.4,9,17Y20 The resuscitation intervals of time that have been evaluated include 6 hours following hospital arrival, 24 hours following hospital arrival, and during surgery. Collectively, these studies demonstrate an association between crystalloid volume and adverse outcomes. It remains unclear, however, whether this association is causative. These studies were not controlled trials, so treatments such as crystalloid administration were at the discretion of individual physicians and driven by clinical decision making with respect to the condition of the patient. This introduces the possibility of confounding by indication, also known as indication bias, whereby statistical association between the treatment of interest (i.e., fluid administration) and outcome (e.g., mortality) is, in fact, caused by the indication for the treatment (i.e., clinical condition prompting decision to give treatment of interest), rather than the treatment of interest itself.21,22 In a recent multi-institutional study, Rahbar et al.23 observed that

TABLE 3. Multiple Logistic Regression for ARDS, 24-Hour Mortality, and In-Hospital Mortality C/PRBC (high ratio) Blunt injury Admission heart rate ISS Admission base excess Hydroxyethyl starch Resuscitation room plasma Resuscitation room platelets Minutes in the resuscitation room

ARDS

24-h Mortality

In-Hospital Mortality

1.43 (0.75Y2.73) 1.70 (0.77Y3.73) 1.00 (0.99Y1.01) 1.05 (1.02Y1.07)* 0.99 (0.93Y1.04) 1.20 (0.60Y2.40) 1.23 (0.91Y1.68) 0.99 (0.57Y1.71) 1.00 (0.99Y1.02)

0.89 (0.49 to 1.63) 0.77 (0.36 to 1.62) 1.00 (0.98 to 1.01) 1.04 (1.02 to 1.06)* 0.95 (0.91 to 1.00)* 1.24 (0.65 to 2.40) 0.94 (0.65 to 1.36) G0.001 (G0.001 to 9999) 1.01 (1.00 to 1.03)

0.89 (0.52Y1.53) 1.00 (0.52Y1.93) 0.99 (0.99Y1.01) 1.05 (1.03Y1.07)* 0.94 (0.90Y0.98)* 1.24 (0.70Y2.22) 0.86 (0.64Y1.16) 0.62 (0.24Y1.60) 1.01 (1.00Y1.03)*

* = p G 0.05. Data presented as ORs with 95% CIs.

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early resuscitation with four or more ‘‘units’’ of any fluid (crystalloid, colloid, blood product) was significantly associated with 6-hour mortality. The authors correctly concluded that early resuscitation intensity is a surrogate marker for illness severity, rather than it being a causative factor contributing to mortality in their cohort. Cognizant of the issue of indication bias, we chose to evaluate the effect of crystalloid use over a very specific interval, that is, the initial trauma bay resuscitation, rather than include relatively longer intervals (such as during hemorrhage control in the operating room), whereby decisions to give crystalloids and/or blood products would necessarily be influenced by the dynamic condition of the patient. Given the findings of the multi-institutional study regarding early resuscitation intensity as described earlier,23 we chose to analyze the use of crystalloid by way of C/PRBC as described by Neal et al.,9 rather than by volume alone, as it would be expected that higher crystalloid volumes would be associated with worse outcome, reflecting the degree of injury and shock despite statistical adjustment for such variables. This was confirmed in an observational study of trauma patients by Ley et al.,17 whereby the authors demonstrated that crystalloid administration of 1.5 L or more in the emergency department was associated with mortality. Despite adjustment for differences in baseline clinical variables such as ISS, their finding was likely related to crystalloid volume being a surrogate for degree of injury, as noted by Rahbar et al.23 In fact, the data from the present study also demonstrated crystalloid volume to be an independent predictor of mortality (adjusted OR, 1.2; 95% CI, 1.08Y1.4), when crystalloid volume was analyzed alternatively as an independent variable and not in the context of a ratio. Evaluation of the crystalloidYtoYred blood cell ratio, rather than the volume of crystalloid in isolation, helps to better address the current controversy over the relative risks and benefits of crystalloids and blood products used during trauma resuscitation. The results of the present study indicate that the relative volume of crystalloid infusion relative to red blood cell transfusion, as administered during initial resuscitation, did not affect subsequent patient outcomes including mortality and ARDS. From our experience, it seems that crystalloid administration in the trauma resuscitation room does not, in fact, result in harm to the patient. The observations of the present study should be interpreted with certain limitations of the study in mind. Despite constructing the study to limit the effect of indication bias as described earlier, it is certain that an element of indication bias remains. Resuscitation at our institution is certainly rooted in Advanced Trauma Life Support guidelines and influenced by current trends, but it is not driven by strict protocol. Therefore, it was not possible to account for differences in individual surgeon practice with respect to resuscitation. In addition, it was not possible to identify and account for specific factors that influenced the decision to give crystalloid and/or blood in these study patients. Adjustment for ISS, age, mechanism of injury, and similar demographic and clinical variables help to account for baseline differences between patient groups, but there are likely more subtle baseline differences among patients that could affect differences in treatment (i.e., balance of crystalloid vs. blood). Factors such as prehospital transport

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time and fluid administration, for example, were not accounted for, and these variables may have influenced decision making during initial resuscitation. Furthermore, while the sample size of the current study was large enough to demonstrate reliable comparisons between variables in the regression analysis with narrow CIs, the possibility that this study lacks the power necessary to show a statistical difference in outcomes is a known limitation. In summary, concern regarding the morbidity associated with high-volume crystalloid use relative to PRBCs may be excessive, particularly with respect to initial resuscitation. In our experience, the ratio of crystalloid to red blood cell transfusion administered during initial trauma resuscitation was not associated with subsequent mortality or pulmonary dysfunction in a cohort of patients that received at least one PRBC unit in the resuscitation room of a Level 1 trauma center. The administration of crystalloid during the initial resuscitation of the trauma patient can therefore not be condemned. AUTHORSHIP J.P.S. and J.A.W. contributed to the data collection, analysis, and interpretation as well as in the drafting of the manuscript. L.J.M. and E.M.P. contributed to the data interpretation and critical revision. T.J.S., M.A.C. and T.C.F. provided critical revision. DISCLOSURE The authors declare no conflicts of interest.

REFERENCES 1. Shires GT. Management of hypovolemic shock. Bull N Y Acad Med. 1979; 55(2):139Y149. 2. Radvinsky DS, Yoon RS, Schmitt PJ, Prestigiacomo CJ, Swan KG, Liporace FA. Evolution and development of the Advanced Trauma Life Support (ATLS) protocol: a historical perspective. Orthopedics. 2012; 35(4):305Y311. 3. Cotton BA, Guy JS, Morris JA Jr, Abumrad NN. The cellular, metabolic, and systemic consequences of aggressive fluid resuscitation strategies. Shock. 2006;26(2):115Y121. 4. Robinson BR, Cotton BA, Pritts TA, et al. Application of the Berlin definition in PROMMTT patients: the impact of resuscitation on the incidence of hypoxemia. J Trauma Acute Care Surg. 2013;75(1 Suppl 1):S61YS67. 5. Dutton RP. Resuscitative strategies to maintain homeostasis during damage control surgery. Br J Surg. 2012;99(Suppl 1):21Y28. 6. Holcomb JB. Damage control resuscitation. J Trauma. 2007;62(Suppl 6): S36YS37. 7. Holcomb JB, Spinella PC. Optimal use of blood in trauma patients. Biologicals. 2010;38(1):72Y77. 8. Cotton BA, Reddy N, Hatch QM, et al. Damage control resuscitation is associated with a reduction in resuscitation volumes and improvement in survival in 390 damage control laparotomy patients. Ann Surg. 2011;254(4): 598Y605. 9. Neal MD, Hoffman MK, Cuschieri J, et al. Crystalloid to packed red blood cell transfusion ratio in the massively transfused patient: when a little goes a long way. J Trauma Acute Care Surg. 2012;72(4):892Y898. 10. Tapia NM, Suliburk J, Mattox KL. The initial trauma center fluid management of penetrating injury: a systematic review. Clin Orthop Relat Res. 2013;471(12):3961Y3973. 11. Balogh Z, McKinley BA, Cocanour CS, et al. Supranormal trauma resuscitation causes more cases of abdominal compartment syndrome. Arch Surg. 2003;138(6):637Y642; discussion 642Y633. 12. Maxwell RA, Fabian TC, Croce MA, Davis KA. Secondary abdominal compartment syndrome: an underappreciated manifestation of severe hemorrhagic shock. J Trauma. 1999;47(6):995Y999.

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13. Arieff AI. Fatal postoperative pulmonary edema: pathogenesis and literature review. Chest. 1999;115(5):1371Y1377. 14. Morrison CA, Carrick MM, Norman MA, et al. Hypotensive resuscitation strategy reduces transfusion requirements and severe postoperative coagulopathy in trauma patients with hemorrhagic shock: preliminary results of a randomized controlled trial. J Trauma. 2011;70(3):652Y663. 15. Duchesne JC, McSwain NE Jr., Cotton BA, et al. Damage control resuscitation: the new face of damage control. J Trauma. 2010;69(4):976Y990. 16. Maegele M, Schochl H, Cohen MJ. An up-date on the coagulopathy of trauma. Shock. 2014;41 Suppl 1:21Y25. 17. Ley EJ, Clond MA, Srour MK, et al. Emergency department crystalloid resuscitation of 1.5 L or more is associated with increased mortality in elderly and nonelderly trauma patients. J Trauma. 2011;70(2):398Y400. 18. Kasotakis G, Sideris A, Yang Y, et al. Aggressive early crystalloid resuscitation adversely affects outcomes in adult blunt trauma patients: an analysis of the Glue Grant database. J Trauma Acute Care Surg. 2013;74(5): 1215Y1221; discussion 1221Y1212. 19. Duchesne JC, Heaney J, Guidry C, et al. Diluting the benefits of hemostatic resuscitation: a multi-institutional analysis. J Trauma Acute Care Surg. 2013; 75(1):76Y82. 20. Guidry C, Gleeson E, Simms ER, et al. Initial assessment on the impact of crystalloids versus colloids during damage control resuscitation. J Surg Res. 2013;185(1):294Y299. 21. Middelburg RA, van de Watering LM, van der Bom JG. Blood transfusions: good or bad? Confounding by indication, an underestimated problem in clinical transfusion research. Transfusion. 2010;50(6):1181Y1183. 22. del Junco DJ, Fox EE, Camp EA, Rahbar MH, Holcomb JB. Seven deadly sins in trauma outcomes research: an epidemiologic post mortem for major causes of bias. J Trauma Acute Care Surg. 2013;75(1 Suppl 1): S97YS103. 23. Rahbar E, Fox EE, del Junco DJ, et al. Early resuscitation intensity as a surrogate for bleeding severity and early mortality in the PROMMTT study. J Trauma Acute Care Surg. 2013;75(1 Suppl 1):S16YS23.

EDITORIAL CRITIQUE The authors have performed an interesting analysis looking at the early crystalloid: packed red blood cell (PRBC) ratio during the resuscitation phase of injury in the trauma bay and its association with pulmonary outcomes and attributable mortality post injury. They appropriately refer to the prior literature on this topic and interpret the current results they have

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appropriately. They utilized a large, single center, prospective dataset over a six year period and calculated and then dichotomized the crystalloid/packed red blood cell ratio (C/PRBC) into high (Q 0.75) and low (G 0.75) groups. Stepwise logistic regression was utilized to determine those strongest risk factors for ARDS, early or in-hospital mortality. Interestingly, a high C/PRBC ratio as defined was not associated with the outcomes of interest for the study which does contradict prior studies on this topic. Although the authors appropriately comment on the limitations of the study and report that crystalloid volume, when characterized alone when not in a ratio with PRBCs, was an independent risk factor for mortality. Importantly, the time course of the study focuses on a 40Y50 minute time period, on average, and the odds ratios demonstrate a negative association with a high a C/PRBC without statistical significance. The first representing a small time period which may correlate poorly with the overall amount of crystalloid a patient receives over a full resuscitation period (12Y24 hours) and the second suggesting that a larger patient population may provide the power to demonstrate a statistically significant relationship. An ever increasing supply of studies continues to demonstrate that the historic crystalloid resuscitation practice of old is both associated with poor outcome and may in part play a causal role for such outcomes. The current short window of resuscitation which occurs in the trauma bay may have no statistical significance in the current study population but when added in with the remaining resuscitative period would likely demonstrate a higher independent risk of pulmonary complications and other attributable outcomes. As this time period only represents a small window into the resuscitation period, caution should be employed when incorporating these results to standard practice. Jason L. Sperry MD, MPH Department of Surgery University of Pittsburgh Pittsburgh, Pennsylvania

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Crystalloid administration during trauma resuscitation: does less really equal more?

Current direction in trauma resuscitation includes emphasis on minimizing crystalloid, along with early transfusion of blood products. Although eviden...
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