[Show abstract][Hide abstract] ABSTRACT: Approximately 10% of military trauma patients and 3% to 5% of civilian trauma patients require massive transfusion, typically defined as greater than 10 units of packed RBCs (pRBCs) within 6 to 24 hours of hospital
admission.1 The protocol for massive transfusion in adult trauma patients is controversial. The traditional approach calls for administration of fresh frozen plasma (FFP) and platelets when there is strong evidence of coagulopathy or after transfusion of greater than 10 units of pRBCs. The competing approach (sometimes called 1:1:1) calls for FFP (prethawed) and platelets to be administered as early as the first unit of pRBCs at an FFP:platelet:pRBC ratio of approximately 1:1:1 to 2 for patients likely to require massive transfusion. Although to our knowledge there have been no published randomized controlled trials to compare the 2 approaches, numerous observational studies have shown an association between 1:1:1 and improved outcome. However, nonexperimental studies are particularly prone to bias, and survivor bias is one of the more serious, interesting, and perhaps less obvious problems in these studies. We have used data from a recent study2 to illustrate the different types of survivor bias (Figure 1). Understanding them improves the quality of discourse about massive
transfusion and may heighten awareness of the presence of survivor bias in other quasi-experimental and
Full-text · Article · Jan 2015 · Annals of Emergency Medicine
[Show abstract][Hide abstract] ABSTRACT: Observational studies on transfusion in trauma comparing high versus low plasma:erythrocyte ratio were prone to survivor bias because plasma administration typically started later than erythrocytes. Therefore, early deaths were categorized in the low plasma:erythrocyte group, whereas early survivors had a higher chance of receiving a higher ratio. When early deaths were excluded, however, a bias against higher ratio can be created. Survivor bias could be reduced by performing before-and-after studies or treating the plasma:erythrocyte ratio as a time-dependent covariate.We reviewed 26 studies on blood ratios in trauma. Fifteen of the studies were survivor bias-unlikely or biased against higher ratio; among them, 10 showed an association between higher ratio and improved survival, and five did not. Eleven studies that were judged survivor bias-prone favoring higher ratio suggested that a higher ratio was superior.Without randomized controlled trials controlling for survivor bias, the current available evidence supporting higher plasma:erythrocyte resuscitation is inconclusive.
[Show abstract][Hide abstract] ABSTRACT: Observational studies on injured patients requiring massive transfusion have found a survival advantage associated with use of equivalent number of units of fresh frozen plasma (FFP) and packed red blood cells (RBCs) compared with use of FFP based on conventional guidelines. However, a survivorship bias might have favoured the higher use of FFP because patients who died early never had the chance to receive sufficient FFP to match the number of RBC units transfused.
A Markov model using trauma data from local hospitals was constructed and various FFP transfusion scenarios were applied in Monte Carlo simulations in which the relative risk of death associated with exposure to high FFP transfusion was set at 1.00, so that the FFP : RBC ratio had no influence on mortality outcome.
Simulation results showed that the relative risk associated with exposure to high FFP transfusion was less than 1.00 (0.33-0.56 based on programmed delays in achieving an FFP : RBC ratio of 1 : 1-2), thus demonstrating a survivorship bias in favour of FFP : RBC equal to or more than 1 : 1-2 in certain observational trauma studies. This bias was directly proportional to the delay in achieving a FFP : RBC ratio of 1 : 1-2 during resuscitation.
Some observational studies comparing low and high FFP administration in injured patients requiring massive transfusion probably involve survivorship bias that inflates or creates a survival advantage in favour of a higher FFP : RBC ratio.
Full-text · Article · Jan 2012 · British Journal of Surgery
[Show abstract][Hide abstract] ABSTRACT: “1:1”
Wethank Professors Fries and Luger for their comments. Indeed,
there is massive confusion on how to administer fresh frozen
plasma (FFP) in trauma patients with massive and ongoing bleeding
Stanworth et al.’s systematic review of studies mostly done
in the era of whole blood as opposed to packed red blood cells
(PRBCs), showing that prophylactic administration of FFP in euvolemic
patients, most of whom had no pre-existing haemostatic
deficiencies, undergoing elective non-exsanguinating procedures
did not lead to reduced blood loss/use2 is again used as a lightning
rod by opponents of the so-called “1:1” strategy in the trauma and
It is true that liberal administration of FFP, or any fluid for
that matter, in a euvolemic patient risks overloading. The topic
of our discussion is, however, on patients who are presenting
with MOB, whose problems include hypovolemic shock and coagulopathy.
The early use of sufficient quantities of FFP, or “1:1”,
would hopefully reduce the likelihood of persistent coagulopathy
after euvolemia is finally restored, and thus prevent the
problem of having to administer large quantities of FFP at that
We agree that albumin is potentially harmful to patients with
head injury, and it would be better to administer target therapy
based on thrombelastography and the use of fibrinogen and
prothrombin complex concentrates. Unfortunately, thrombelastography
and factor concentrates are not available in emergency
or operating rooms in many parts of the world. We do appreciate
the acknowledgement that there is a need to replace coagulation
factors, which, in many countries, still come mainly in the form of
Citrate toxicity occurs with rapid transfusion of large quantities
of blood products. It is easily recognized, monitored, treated, and is
seldom a significant consideration in the decision making process
for us when transfusing blood products.
FFP is implicated in TRALI, although other blood products are
not entirely innocent. There are two questions that need to be
answered. First, does the aggressive use of FFP to achieve an
FFP:PRBC ratio of almost 1:1 early on in trauma patients with MOB
result in higher use of blood products? Second, does “1:1”, again in
trauma patients with MOB, result in more TRALI, respiratory failure,
sepsis, or most importantly, higher mortality rate?
On the first question, we refer our readers to studies showing
that “1:1” results in the same or reduced amount of exposure
to blood products.3–5 On the second question, we refer to studies
showing “1:1” improves survival.6–8 Not all studies show that “1:1”
is superior in the trauma with MOB setting, but the vast majority
of them do.
On survivorship bias (SB), Snyder et al.’s study purportedly
showed that when observational data were analyzed in a way to
eliminate SB, the survival benefit of “1:1” did not reach statistical
significance.9 We agree that a significant proportion of observational
studies on “1:1” are susceptible to SB. Nonetheless, we wish
to point out that Snyder et al.’s study was possibly underpowered,
and their non-“1:1” and “1:1” groups were not independent.
Patients were transitioning from the former to the latter group
almost entirely unidirectionally during the course of resuscitation.
That tells us that clinicians in the study were responding to ongoing
bleeding and serious coagulopathy by giving FFP. In other words, as
we argue the merits of “1:1”, our front line colleagues are already
“doing it”. It is quite possible that when a patient transitions from
a low FFP to “1:1”, he is also bringing the perils of excessive coagulopathy
from the former cohort to the latter. In other words, if “1:1”
is superior, we do not expect that it could immediately deliver that
advantage as soon as that magic ratio is reached – it could already
be too late.
Which brings us to another bias, confounding by indication. In
centres without an aggressive FFP transfusion protocol, it is those
patients who have more severe bleeding and coagulopathy that
tend to get more FFP in an observational study.
Staying with SB, one way to reduce that bias is the use of
two entirely different and independent cohorts. Numerous authors
have compared outcomes between patients before and after the
implemention of a “1:1” protocol and have found “1:1” to be clearly
superior.4–6,10 Granted that resuscitation techniques must have
progressed for the better to have explained the better outcomes
enjoyed by the “after” group, we should at least acknowledge that
perhaps that “1:1” is a component of that progression for the better.
Riskin et al.’s study5 is particularly worth a close look. They
found that the FFP:PRBC ratios were identical before and after
implementaion of a “1:1” protocol. The only difference was that
“1:1” led to an earlier use of FFP. The lesson there is that you can
give FFP earlier proactively, or you can give it later reactively. Either
way, you will wind up giving a lot of FFP, except that playing “catch
up” has a serious price to pay in terms of outcome.
It is a good thing no one has done observational studies on
whether surgery is useful in trauma patients with MOB, otherwise
surgery would also have been found to have “benefitted”
from SB, and, with all of its attending side-effects of infection,
bleeding, immunologic suppression, pain, scarring, etc., dismissed
On the issue of volume replacement with the newest types of
synthetic colloids, hydroxyethyl starch 130/0.4-0.42/6 comes to
mind. There is a dose limit of 50 mL/kg because of dose-dependent
adverse haemostatic effects.
Prof. Fries and Luger ask, was it the volume effect of FFP or
was it the coagulation factors that bring increased survival? We
gratefully acknowledge their tacit agreement that FFP given appropriately
aggressively in trauma patients with MOB does seem to be useful. For now, to a frontline colleague, that is all he
“1:1” is balanced; any major deviation from this ratio represents
an intrinsically anaemic or factor-deficient mixture. As mentioned
earlier, frontline clinicians are already “doing it”. That does not necessarily
mean that they are right, but disregarding the power of
observations of somanyexperienced clinicians and studies because
of statistical and methological imperfections, is not right either.
Ultimately, perhaps a better question than asking if “1:1” is good
is this: Next time an exsanguinating trauma patient presents, what
mixture are you going to give?
Conflict of interest statement
None to declare.
1. Ho AMH, Dion PW, Yeung JH, et al. Fresh-frozen plasma transfusion strategy
in trauma with massive and ongoing bleeding Common (sense) and sensibility.
2. Stanworth SJ, Brunskill SJ, Hyde CJ, et al. Is fresh frozen plasma clinically
effective? A systematic review of randomized controlled trials. Br J Haematol
3. Dente CJ, Shaz BH, Nicholas JM, et al. Improvements in early mortality and coagulopathy
are sustained better in patients with blunt trauma after institution
of a massive transfusion protocol in a civilian level I trauma center. J Trauma
4. Gunter Jr OL, Au BK, Isbell JM, et al. Optimizing outcomes in damage control
resuscitation: identifying blood product ratios associated with improved survival.
J Trauma 2008;65:527–34.
5. Riskin DJ, Tsai TC, Riskin L, et al. Massive transfusion protocols: the role of aggressive
resuscitation versus product ratio in mortality reduction. J Am Coll Surg
6. Cotton BA, Au BK, Timothy C, et al. Predefined massive transfusion protocols
are associated with a reduction in organ failure and postinjury complications. J
7. Sperry JL, Ochoa JB, Gunn SR, et al. An FFP:PRBC transfusion ratio ≥1:1.5 is
associated with a lower risk of mortality after massive transfusion. J Trauma
8. Watson GA, Sperry JL, Rosengart MR, et al. Fresh frozen plasma is independently
associated with a higher risk of multiple organ failure and acute respiratory
distress syndrome. J Trauma 2009;67:221–30.
9. Snyder CW, Weinberg JA, McGwin Jr G, et al. The relationship of blood product
ratio to mortality: survival benefit or survival bias? J Trauma 2009;66:
10. Zaydfudim V, Dutton WD, Feurer ID, et al. Exsanguination protocol improves
survival after major hepatic trauma. Injury 2010;41:30–4.
Anthony M.-H. Hoa,∗
Peter W. Dionc
Calvin S.H. Ngb
Chi Wai Cheungd
Janice H.H. Yeunge
Lester A.H. Critchley a
a Department of Anaesthesia and Intensive Care, The
Chinese University of Hong Kong, Hong Kong
b Department of Surgery, The Chinese University of
Hong Kong, Hong Kong
c Department of Anaesthesia, St. Catharines General
Hospital, Hong Kong
d Department of Anaesthesiology, The University of
Hong Kong, Hong Kong
e Accident and Emergency Department, Prince of
Wales Hospital, Hong Kong
∗ Corresponding author at: Department of
Anaesthesia and Intensive Care, Prince of Wales
Hospital, Shatin, NT, Hong Kong.
Tel.: +852 26321133; fax: +852 26372422.
E-mail addresses: email@example.com,
firstname.lastname@example.org (A.M.-H. Ho)
16 December 2010
[Show abstract][Hide abstract] ABSTRACT: During trauma resuscitation involving massive transfusion, the best fresh-frozen plasma to packed red blood cells ratio is unknown. No randomised controlled trial (RCT) is available on this subject, although there are plenty of observational studies suggesting that the ratio should be about 1:1. This ratio also makes more physiological sense, and we suggest that in patients with massive and ongoing bleeding, it is a sensible strategy with which to start resuscitation.
[Show abstract][Hide abstract] ABSTRACT: Problems in projectile motion are a time-honored staple of high school
and even first-year university physics. They can become confusing for
some students, yet boring for the stronger students. Herein we present
two alternative approaches to such questions, one we call ``breaking
down gravity,'' which makes these questions easier to solve, and the
other we call ``getting rid of gravity,'' which converts such questions
into a more interesting and challenging form.
No preview · Article · Jan 2010 · The Physics Teacher
[Show abstract][Hide abstract] ABSTRACT: Airway, breathing, and circulation are top priorities in any resuscitation. However, in cardiac tamponade, the decision to intubate the trachea and initiate positive pressure ventilation (PPV) should only be taken after consideration of the deleterious haemodynamic effects of positive intrathoracic pressure. We suggest that the threshold for intubation and PPV should be raised in tamponade and that intubation and PPV should, if possible, be timed so that relief of tamponade can immediately follow. In the trauma setting, emergency thoracotomy is the best approach. When intubation is unavoidable because of very low oxygen saturation or cardiac arrest, high ventilatory pressures should be avoided.
[Show abstract][Hide abstract] ABSTRACT: The laryngeal mask airway (LMA) is now standard airway management equipment in prehospital and Emergency Department (ED) care. Most providers may not be able to match the pediatric LMA sizes to the appropriate weights of pediatric patients. The exact inflation volumes are also difficult to memorize. To overcome this problem, we propose the following equations: Weight (kg) of patient = 2(2 x LMA), where LMA is the size; cuff inflation volume (mL) = 5 x LMA.
Full-text · Article · Jun 2008 · Journal of Emergency Medicine
[Show abstract][Hide abstract] ABSTRACT: Randomized controlled trials of how best to administer fresh frozen plasma (FFP) in the presence of ongoing severe traumatic hemorrhage are difficult to execute and have not been published. Meanwhile, coagulopathy remains a common occurrence during major trauma resuscitation and hemorrhage remains a major cause of traumatic deaths, suggesting that current coagulation factor replacement practices may be inadequate.
We used a pharmacokinetic model to simulate the dilutional component of coagulopathy during hemorrhage and compared different FFP transfusion strategies for the prevention or correction, or both, of dilutional coagulopathy. Assuming the rates of volume replacement and loss are roughly equal, we derived the hematocrit and plasma coagulation factor concentration over time based on the rate of blood loss and replacement, the hematocrit and coagulation factor concentration of the transfusate, and the hematocrit and plasma factor concentration at the time when FFP transfusion begins.
Once excessive deficiency of factors has developed and bleeding is unabated, 1-1.5 units of FFP must be given for every unit of packed red blood cells (PRBC) transfused. If FFP transfusion should start before plasma factor concentration drops below 50% of normal, an FFP:PRBC transfusion ratio of 1:1 would prevent further dilution.
During resuscitation of a patient who has undergone major trauma, the equivalent of whole-blood transfusion is required to correct or prevent dilutional coagulopathy.
Full-text · Article · Jan 2006 · Canadian journal of surgery. Journal canadien de chirurgie
[Show abstract][Hide abstract] ABSTRACT: Continuous central pressure monitoring and simultaneous continuous infusion via the same central venous catheter are sometimes necessary. Based on theoretical calculations and experimental measurements, we have determined that pressure monitoring is essentially unaffected if the continuous infusion rate is 50 ml.h(-1) or less for an adult and a paediatric central catheter. At rates > 200 ml.h(-1), the central venous pressure is exaggerated by up to 4 mmHg and 8 mmHg for the adult and paediatric catheters, respectively.
[Show abstract][Hide abstract] ABSTRACT: Hemorrhage is a major cause of trauma deaths. Coagulopathy exacerbates hemorrhage and is commonly seen during major trauma resuscitation, suggesting that current practice of coagulation factor transfusion is inadequate. Reversal of coagulopathy involves normalization of body temperature, elimination of the causes of disseminated intravascular coagulation (DIC), and transfusion with fresh-frozen plasma (FFP), platelets, and cryoprecipitate. Transfusion should be guided by clinical factors and laboratory results. However, in major trauma, clinical signs may be obscured and various factors conspire to make it difficult to provide the best transfusion therapy. Existing empiric transfusion strategies for, and prevailing teachings on, FFP transfusion appear to be based on old studies involving elective patients transfused with whole blood and may not be applicable to trauma patients in the era of transfusion with packed red blood cells (PRBCs). Perpetuation of such concepts is in part responsible for the common finding of refractory coagulopathy in major trauma patients today. In this review, we argue that coagulopathy can best be avoided or reversed when severe trauma victims are transfused with at least the equivalent of whole blood in a timely fashion.
Full-text · Article · Oct 2005 · The American Journal of Surgery