Civilian Trauma Hemorrhage Permissive Hypotension Predefined
Search Strategy: You conduct three PUBMED searches. First, using the term “blood products combat ratio” you obtain 14 citations (see http://tinyurl.com/732ghfo). Second, you conduct a PUBMED search for “transfusion combat trauma” and identify 103 citations (see http://tinyurl.com/7mvd8md). Third, you search PUBMED using the search term “hypotensive resuscitation mortality” finding 133 citations (see http://tinyurl.com/7gfcltg). You select the four articles below for closer review.
As the senior medical officer in a U.S. military Combat Support Hospital in Afghanistan, you receive word of incoming wounded from a massive IED blast that took out several vehicles. Over the next 90-minutes 25 patients arrive of which 5 are triaged as black (expectant), 12 as red (emergent), and the rest as walking wounded. You mobilize your resources to treat and stabilize the emergent patients. Ultimately, you are able to resuscitate six of the patients all of whom are then sent to the main hospital for definitive care. Job well done.
Once all is quiet on the western front, one of the physicians who has recently arrived from a prestigious stateside EM training program pulls you aside to ask why you did not vigorously hydrate your patients and why you “wasted” a lot of blood? After taking him outside to make him “drop and give you twenty”, you decide a more academic approach is in order and have him review articles regarding Damage Control Resuscitation, specifically addressing permissive hypotension and transfusion protocols. In addition, you assign him a Journal Club the next day during the Army Surgeon General’s visit to the hospital.
PICO Question #1
Population: Military personnel with severe penetrating or blunt trauma
Intervention: Permissive hypotension
Comparison: Blood pressure directed fluid resuscitation
Outcome: Mortality, long-term morbidity (end-organ damage, blood-product related infections)
PICO Question #2
Population: Military personnel with severe penetrating or blunt trauma and hypotension/ongoing hemorrhage
Intervention: Massive transfusion protocols
Comparison: Packed red blood cell transfusions alone
Outcome: Mortality, bleeding complications, iatrogenic volume overload
Second years: 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: 652-663. (http://pmid.us/21610356)
Third years: Effect of plasma and red blood cell transfusions on survival in patients with combat related traumatic injuries, J Trauma 2008; 64: S69-S78. (http://pmid.us/18376175)
Fourth years: Early aggressive use of fresh frozen plasma does not improve outcome in critically injured trauma patients, Ann Surg 2008; 248: 578-584. (http://pmid.us/18936570)
Article 1: Hypotensive resuscitation during active hemorrhage: impact on in-hospital mortality, J Trauma 2002; 52: 1141-1146.
Article 2: 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: 652-663.
Article 3: Effect of plasma and red blood cell transfusions on survival in patients with combat related traumatic injuries, J Trauma 2008; 64: S69-S78.
Article 4: Early aggressive use of fresh frozen plasma does not improve outcome in critically injured trauma patients, Ann Surg 2008; 248: 578-584.
Trauma is the leading cause of death in young adults and hemorrhage is a leading cause of traumatic mortality (Sørcide 2009). In fact, about one-third of trauma deaths occur because the victim bleeds to death within the first few hours post-injury (Kauvar 2006). In combat settings, autopsies reveal that up to 20% of deaths are preventable with 80% of these deaths due to hemorrhagic shock (Bellamy 1984, Holcomb 2007). The key ATLS management strategy for hemorrhagic shock has traditionally been rapid fluid resuscitation, but aggressive fluid infusions in multiple animal models leads to increased bleeding and decreased survival (Stern 1993, Kowalenko 1992, Bickell 1991, Riddez 1998, Burris 1999, Sakles 1997, Smail 1998). In the 1990’s one randomized trial (pre-hospital fluids or no fluids) in penetrating trauma victims demonstrated a survival advantage in the “no fluids” group (Bickell 1994).
The deadly triad of hypothermia, hemodilution, and acidosis is well recognized in hemorrhagic trauma (Ferrara 1990, Cosgriff 1997), but decades-old management strategies create a “blood vicious cycle” nonetheless. Excessive crystalloid resuscitation in hemorrhagic trauma is associated with suboptimal outcomes (Cotton 2006) and red blood cell (RBC) transfusions are independently associated with increased morbidity and mortality in critically ill patients (Moore 1997, Malone 2003). In addition, the age of stored RBC’s is an important (yet often unmeasured) variable since there is insufficient evidence that stored RBC’s improve oxygen delivery (Tinmouth 2006, Ho 2003, Marik 1993). Transfusion of older RBC’s is associated with an increased risk of organ failure and mortality (Purdy 1997,Zallen 1999). One controversial solution for aging RBC’s in the military is fresh whole blood (Kauvar 2006).
Trauma Surgery identified the literature we reviewed as the highest quality research on these topics. Our analyses:
Dutton et al provide inconclusive results for several reasons. First, selection and co-intervention biases are real possibilities since their very specific (male, inner city, no CNS injuries, under age 55-years, non-pregnant) patient population receives care in a renowned trauma center. Second, the effects of hemorrhage control interventions (interventional radiology, surgery) cannot be estimated since the type and quantity of these interventions are not reported. Third, without a power calculation these results have a high likelihood for a Type II error. This was not a non-inferiority or equivalence trial. Therefore, this research neither supports nor refutes permissive hypotension in hemorrhaging blunt and penetrating trauma victims. Less biased trial designs are needed utilizing CONSORT methods and acceptable metrics for tissue hypoperfusion before we should re-write ATLS guidelines or alter current bedside practice.
Morrison et al applies tangentially to ED management since this Houston protocol dictated a “no-fluid” pre-hospital and ED resuscitation strategy before testing intra-operative hypotensive (target MAP 50) resuscitation strategies administered by anesthesiology in non-pregnant young adult trauma victims with SBP <90. Their results imply that permissive hypotension may be a safe strategy that does not increase mortality and concurrently reduces the consumption of blood products. Future research efforts should follow CONSORT methods, evaluate patient-centric outcomes, and provide an assessment of similar lower target blood pressure management in pre-operative EMS and ED settings. Unfortunately, these results cannot be extrapolated to pregnant or middle-aged/geriatric populations.
RBC:FFP 1:1 Transfusion Ratios
Although the chart review methods are insufficient and the external validity of combat casualty trauma care to civilian populations is very questionable, the findings of Spinella et al imply that in warzone trauma victims who receive any blood products, transfusion of plasma was independently associated with improved survival whereas RBC transfusions alone decrease survival.
Scalea et al. demonstrated that the mortality benefits observed with aggressive transfusion of FFP in military settings do not extrapolate to civilian settings. There are several possible explanations for these findings, including:
- Differing injury patterns
- Differing injury severity not captured by the Injury Severity Score
- Survival bias whereby the sickest civilians do not survive to the hospital as do healthy young military personnel
- Resources are available in the United States-based trauma center (interventional radiology, trauma surgery, trauma anesthesiology) are less likely to be available in the wartime theatre.
Advising widespread adoption of one-to-one PRBC to FFP is unwarranted since there is no convincing evidence that outcomes will improve. In addition, such a paradigm shift towards massive transfusion protocols in the civilian setting would undoubtedly strain blood bank resources. A subset of trauma patients who will benefit from plasma and FFP in set ratios likely exists, but that population has yet to be identified.