Despite ongoing advances in resuscitative medicine, the determination of the optimal methods and goals of resuscitation remain elusive and an area of intense controversy. (27
) As the concept of ‘damage control resuscitation’ has slowly but steadily grown in popularity over the past decade and a half, it has become increasingly clear that while immediate and aggressive fluid resuscitation of the injured victim may rapidly improve the vital signs of both patient and treating physician, the overall effect on outcome may be much less comforting. (27
) The physician in charge of the resuscitation efforts must remain mindful of the post-traumatic and dilutional coagulopathy (10
), iatrogenic volume overload (9
), and the myriad complications stemming from the physiologic and immunologic effects of large volume resuscitation and massive blood product transfusion strategies. (16
As a growing body of evidence points to significant morbidity associated with even moderate volumes of crystalloid (4
) or blood component therapy (27
) in a variety of clinical settings, we aimed to determine the effect of crystalloid resuscitation on clinically relevant outcomes and complications in adult blunt trauma victims, the most frequent recipient population of such resuscitation efforts. While we did not find an association between volume of crystalloid resuscitation and mortality, our primary outcome measure, significant associations were noted between crystalloid volume infused during the first post-injury day and highly morbid complications, such as ALI/ARDS, MOF, abdominal and extremity compartment syndromes, and even infectious complications, notably bloodstream and surgical site infections, that we believe will form the first step toward abandoning overly aggressive resuscitation protocols from trauma practices worldwide. We were not able to identify an association between crystalloid volume and mortality even when we included all deaths in our exploratory analysis, as early mortality was noted to be related mainly to injury burden, and not resuscitation. However, all remaining associations became stronger as the denominator decreased - patients still alive at 48 hours (one would have to be alive to develop a complication).
While associative relationships between resuscitative components and adverse outcomes have been previously described, (27
) controversy persists over whether these relationships constituted a mere surrogate for injury severity or represented a truly causative effect. In other words, what has so far been unclear is whether sicker patients with greater injury burden went on to develop various complications as a result of their trauma-induced physiologic derangements, and not due to the massive resuscitation they received. To answer that question, we controlled for both injury severity and acute physiologic derangement, as well as preexisting comorbidities, age and neurologic status, all well-recognized markers of unfavorable outcomes. We also controlled for colloid and blood component administration, as those have been recently associated with adverse outcomes in trauma victims.
We elected to use the multi-institutional Glue Grant cohort for our secondary analysis, as we believe it represents the most accurate, extensive and well-validated prospectively collected dataset for the population of interest. In contrast to previously published efforts that have used 12h resuscitation volumes, (27
) we elected to analyze resuscitation administered over the first 24h. The rationale behind this decision was to ensure that acute resuscitation is complete and would be more indicative of future fluid-related complications, should such associations be identified, as a 12h window would be too narrow for such determinations, as frequently resuscitation is still ongoing, especially in the case of distant pre-hospital transfers or lengthy surgical interventions. We also elected to omit platelet transfusions from our analysis, as the majority of the Glue Grant cohort did not receive any platelet component therapy, and the majority of those who did, received only one unit. We also wanted to maintain power in our regression model to the extent possible, ensuring inclusion of well-recognized confounders associated with adverse outcomes, as well as other more commonly used blood component therapy, so their effect would be controlled for in our analysis. A separate outcomes analysis associated with blood component therapy in the blunt trauma population is currently under way.
After dividing our cohort into four distinct crystalloid volume groups so we could arrive at more meaningful and clinically memorable conclusions, we noted some differences between the baseline characteristics across the four groups. Interestingly enough, age and comorbidities appeared to be lower in the higher volume resuscitation groups, while severity of neurologic injury (scene GCS) remained fairly constant across resuscitation groups. And although injury severity and acute physiology scores rose – as expected – across the four groups, the differences only in the latter reached statistical significance in our analysis of variance (). Also, even though base deficit appeared to be significantly higher in the larger volume groups, the differences were not necessarily clinically significant (BD difference between the <5 L and the > 15 L groups was 2 points).
While the major difference in the baseline characteristics across the various volume groups was noted in APACHE II, ventilator days, ICU and hospital LOS were significantly higher in the subgroups that received larger crystalloid volumes (). Dramatic increases were also noted in the incidence of ALI/ARDS, MOF, compartment syndromes and BSI and SSI in the higher volume groups, and these differences did reach statistical significance on analysis of variance. Interestingly, even after controlling for the aforementioned confounders, the incidence of ALI/ARDS and MOF was significantly higher in the higher volume groups, as was that of abdominal compartment syndrome, a complication well recognized to be tightly associated with higher resuscitation volumes. In fact, the Odds Ratio for development of ALI/ARDS and MOF was three times higher in the >15 L volume group, even after adjusting for severity of injury and physiologic derangement, as well as blood component therapy, likely suggesting a causative mechanism. It is likely the highly acidic nature of the fluids most commonly used in acute trauma resuscitation (normal saline and lactated ringer's) trigger a dose-dependent acute inflammatory response that, not dissimilarly from other highly inflammatory conditions known to be associated with ALI/ARDS and MOF, may easily affect the pulmonary parenchyma as it spirals out of control. (16
) It is also possible that vascular overdistention from volume overload accentuates this phenomenon from local endothelial damage unrelated to the original traumatic insult. (15
Not surprisingly, incidence of abdominal compartment syndrome rose dramatically in the higher volume groups, while extremity compartment syndrome lost significance in our controlled analysis, suggesting that for the development of the latter, voluminous fluid resuscitation must act synergistically with a primary local injury for the clinical syndrome to develop, unlike the case of abdominal compartment syndrome, where high volumes alone may lead to this extremely morbid complication.
One of the most intriguing findings in our study was the higher incidence of surgical site and bloodstream infections in the larger crystalloid volume groups, even though the latter barely missed statistical significance (p=0.056) in our adjusted analysis. The incidence of the former rose from 8% and 4.6% respectively to 20.9% with higher volumes of resuscitation, for an adjusted Odds Ratio of nearly 3 in the subgroup that received >15L of crystalloids. Perhaps, higher volumes of resuscitation bear a previously unrecognized immunomodulatory, or even immunocompromising effect that renders the body less capable of fighting infectious insults. It is interesting, however, that the elevated risk for infectious complications did not translate to significantly higher risk for VAP. Not surprisingly, the number of UTIs (13-15%) and the incidence of ARF (0-2%) remained rather stable across volume groups, as larger fluid volumes improved filtration rates and bestowed a protective effect on the kidneys.
Despite the use of statistical models to the best of our ability to adjust for injury severity, baseline patient characteristics and concomitant resuscitation with blood products, to fully account for the complex interactions between injury and outcome and the medical interventions in-between, as previously described by Klein et al remains challenging. (7
) However, we believe this is a firm attempt at demonstrating the potential adverse outcomes excessive fluid resuscitation may confer, as these complex interactions will continue to be in place, and urge the medical community with the privilege to care for the injured to refrain from it, until well-designed randomized studies shed more light on the optimal method and goals of resuscitation and help develop optimal resuscitation strategies and protocols.