Recent data from the US Army’s Institute of Surgical Research have shown improvement in outcomes when soldiers requiring MTs received resuscitations with ratios of component types that were similar to whole-blood transfusions.40,41
Subsequent reports, primarily in the military literature, further supported a component therapy transfusion in ratios of 1 U pRBC/1 U plasma/1 random donor unit of PLTs.6,24,42,43
Casualties who received less than 1 U of plasma for every 4 U of pRBC were associated with a 65% mortality, whereas those who received 2 U of plasma for every 3 U of pRBCs were associated with 19% mortality.9
The military data have the strength of large numbers of casualties requiring MT. However, these are retrospective studies, and soldiers who died before receiving sufficient (intended) thawed plasma were grouped in the low ratio group, hence introducing a survivorship bias.6,24,42,43
The military data also lacked adjustment for confounding variables with mortality, such as injury severity.6,24,42,43
It is interesting to note that, in one of the military studies, although the goal was a ratio of 1:1, the patients more commonly reached a ratio of 3:2, which is also the ratio supported as an optimum minimum ratio by computer models to avoid dilutional hemorrhage.15,44
Nevertheless, these data have led to widespread support of this ratio, particularly the 1:1 ratio of pRBC/plasma, although considerable debate remains on this topic.26,39,45
Civilian trauma studies (a portion of which are summarized in ) have also evaluated the impact of more aggressive ratios and noted an association with improved survival with use of MTPs.22,33,46,47
Similar to military data, such studies also support using a more aggressive pRBC/plasma ratio, albeit the precise ratio varied significantly among groups.48
The use of a pRBC/plasma ratio between 3:2 and 1:1 (n = 196) resulted in a significant reduction (41% vs 62%) in 30 day mortality as compared with those that received less plasma.37
In that study, an increased odds of survival was associated with an increased intraoperative pRBC/plasma ratio between 3:2 and 1:1.37
This was independent of age and Trauma Related Injury Severity Score, which by themselves were independent predictors of mortality as well.37
The same study favored a PLT ratio of 1 pRBC: 1 random donor pool (or 5 pRBCs: 1 aPLT).37
Interestingly, while the intraoperative product use was higher than the non-MTP group, the 24-hour overall blood component usage was significantly lower as a result of statistically significantly lower utilization of PLTs in the MTP arm (6.8 vs 3.1, P
< .001). The postoperative PTT and PLT counts, available only on a subset of study patients, were also significantly better in the MTP versus non-MTP cohort (39 vs 33 seconds, P
= .38; PLT count 136 vs 96, P
= .001; B.A.C., unpublished data). The intraoperative crystalloid use was also significantly lower in the MTP arm (6.7 vs 4.9 L, P
There is also some anecdotal evidence that MTPs may more effectively manage acidemia and normalize lactate levels in trauma patients (B.A.C. and P.P.Y., unpublished observations).
Studies Evaluating the Impact of an MTP on Outcomes in Trauma Patients
A similar 3:2 pRBC/plasma ratio was used in an MTP protocol for postpartum hemorrhage in obstetric patients.7
Dente and colleagues47,49
evaluated an MTP for civilian trauma patients designed to achieve a pRBC/plasma ratio of 1:1. Although a ratio of 1:1 was their goal, their MTP patients actually received a 3:2 pRBC/plasma ratio, whereas the non-MTP arm received a 3:1 pRBC/plasma ratio. Among blunt trauma patients, the MTP group (with higher plasma portions) exhibited significantly lower 24-hour and 30-day mortality than a control cohort with similar injury severity scores and less plasma. Early crystalloid use was also significantly less in the MTP group.49
Johansson et al50
demonstrated that patients with severe bleeding secondary to ruptured aortic aneurysms showed improved survival when treated with 1:1 ratio of pRBC to plasma.
However, several studies have called into question the benefit of higher ratios.46,51
Shortly after military and civilian data advocated for earlier use and higher ratios of plasma products in MT patients, Kashuk et al46
argued against such ratios. In their study, patients receiving pRBC to plasma in a ratio between 2:1 and 1:1 had a lower 30-day mortality, whereas those with 1:1 had higher mortality. The authors proposed that while patients may benefit from more plasma, aiming for 1:1 was not beneficial and was, in fact, associated with higher mortality. Notably, their study included 133 patients, of which only 11 patients achieved a 1:1 ratio. More recently, Snyder et al51
suggested that the results of studies evaluating the impact of damage control resuscitation and their associated higher ratios of products may have found benefit solely through “survival bias.” However, many of the recent studies examining MTPs and higher ratios actually exclude patients that (1) do not survive the initial operation and resuscitation (approximately the first 3 hours) and (2) do not receive at least 10 U of products before death, specifically to reduce the role of “survival bias” impact on outcome.33,37,39,52
Beyond the impact on survival, there are data to suggest that MTPs shorten both the time for delivery of first shipment of products as well as delivery of subsequent shipments to the bedside.25,34
As mentioned above, the aggressive, early administration of a predesigned complement of blood products also appears to decrease overall blood use and therefore, blood component costs,33,34
if not survival.53
Studies are needed to evaluate these aspects of MTP use.
Although a previously published poll of trauma centers found established protocols in a relatively small number of well-organized centers,54
it is likely that an increasing number of transfusion services, especially those with trauma centers, have a defined MTP. Although such protocols have been associated with improved survival, it is important to assess the data carefully because many centers with MTPs have a history of poor compliance during active resuscitations.11,15,37,49,54
As noted previously, Borgman et al15
noted that while the intended ratio for delivered products was 1:1:1 (pRBC/plasma/random donor PLT unit), fewer than 20% of patients actually received these ratios. Similarly, only one third of patients in a recent civilian study received the predefined ratios of plasma, and fewer than a quarter received the specified PLT ratios.11
More concerning was the finding that failure to achieve these ratios was associated with higher mortality in both military and civilian settings.11,15,37
Thus, when evaluating MTPs, both the protocol and the compliance should be considered before making any conclusions about patient outcomes. Moreover, the timing of activation (ie, whether the protocol is proactively activated early in resuscitation versus late) will likely impact the type of components needed and may have an impact on patient outcomes as well. These findings suggest that multidisciplinary oversight and training should include representatives from transfusion medicine, surgery (in particular, the trauma service), anesthesiology, and critical care to ensure that a well-designed MTP is actually utilized as intended. Additional guidance in the literature on how to develop such oversight strategies would be valuable.
In summary, the cumulative data support early, proactive support with high ratios of plasma to pRBC along with additional support with PLTs.26,39
Not all studies showed a mortality benefit, and in the absence of randomized trials, data to convincingly support a particular ratio or formula are needed. However, the existing data suggest that a well-organized MTP protocol that is activated in a timely fashion is likely to demonstrate improved patient outcomes and result in less overall blood product usage in large trauma centers.