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J Trauma Acute Care Surg. Author manuscript; available in PMC 2022 August 01.
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Published in final edited form as:

J Trauma Acute Care Surg. 2021 August 01; 91(2): 272–278. doi:10.1097/TA.0000000000003251.

Dose-dependent association between blood transfusion and

nosocomial infections in trauma patients: A secondary analysis
of patients from the PAMPer trial
Husayn A. Ladhani, MD,
Division of Trauma, Critical Care, Burns, and Acute Care Surgery, Department of Surgery,
MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio
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Vanessa P. Ho, MD, MPH,

Division of Trauma, Critical Care, Burns, and Acute Care Surgery, Department of Surgery,
MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio

C. Clare Charbonnet, MD,

Division of Trauma, Critical Care, Burns, and Acute Care Surgery, Department of Surgery
MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio

Jason L. Sperry, MD, MPH,

Department of Surgery and Critical Care Medicine, University of Pittsburgh Medical Center,
Pittsburgh, Pennsylvania

Francis X. Guyette, MD, MPH,

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Department of Emergency Medicine, University of Pittsburgh Medical Center, Pittsburgh,

Pennsylvania

Joshua B. Brown, MD, MSc,

Department of Surgery and Critical Care Medicine, University of Pittsburgh Medical Center,
Pittsburgh, Pennsylvania

Brian J. Daley, MD, MBA,

Department of Surgery, University of Tennessee Health Science Center, Knoxville

Richard S. Miller, MD,

Department of Surgery, John Peter Smith Hospital, Fort Worth, Texas

Brian G. Harbrecht, MD,

Department of Surgery, University of Louisville, Louisville, Kentucky
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Herb A. Phelan, MD, MSCS,

Address for reprints: Jeffrey A Claridge, MD, MS, Division of Trauma, Critical Care, Burns, and Acute Care Surgery, Department of
Surgery, MetroHealth Medical Center, 2500 MetroHealth Dr, Cleveland, OH 44109; jclaridge@metrohealth.org.
AUTHORSHIP
All authors have seen and approved the final article as submitted. H. A. L., V. P. H., C. C. C., and J. A. C. performed the literature
review. H. A. L., V. P. H., C. C. C., J. L. S., F. X. G., and J. A. C. participated in the conception and design. All authors participated in
the acquisition of data, analysis and interpretation of data, article preparation, and critical revisions.
This study was presented at 34th Eastern Association for the Surgery of Trauma Annual Scientific Assembly, January 13–14, 2021,
held virtually.
 Ladhani et al. Page 2

Department of Surgery, Louisiana State University Health Sciences Center, New Orleans,
Author Manuscript

Louisiana

Jeffrey A. Claridge, MD, MS,

Division of Trauma, Critical Care, Burns, and Acute Care Surgery, Department of Surgery,
MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio

The PAMPer Study Group

Abstract
BACKGROUND: The Prehospital Air Medical Plasma (PAMPer) trial demonstrated a survival
benefit to trauma patients who received thawed plasma as part of early resuscitation. The objective
of our study was to examine the association between blood transfusion and nosocomial infections
among trauma patients who participated in the PAMPer trial. We hypothesized that transfusion
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of blood products will be associated with the development of nosocomial infections in a dose-
dependent fashion.

METHODS: We performed a secondary analysis of prospectively collected data of patients in the

PAMPer trial with hospital length of stay of at least 3 days. Demographics, injury characteristics,
and number of blood products transfused were obtained to evaluate outcomes. Bivariate analysis
was performed to identify differences between patients with and without nosocomial infections.
Two logistic regression models were created to evaluate the association between nosocomial
infections and (1) any transfusion of blood products, and (2) quantity of blood products. Both
models were adjusted for age, sex, and Injury Severity Score.

RESULTS: A total of 399 patients were included: age, 46 years (interquartile range, 29–59
years); Injury Severity Score, 22 (interquartile range, 12–29); 73% male; 80% blunt mechanism;
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and 40 (10%) deaths. Ninety-three (27%) developed nosocomial infections, including pneumonia
(n = 67), bloodstream infections (n = 14), catheter-associated urinary tract infection (n = 10),
skin and soft tissue infection (n = 8), Clostridium difficile colitis (n = 7), empyema (n = 6), and
complicated intra-abdominal infections (n = 3). Nearly 80% (n = 307) of patients received packed
red blood cells (PRBCs); 12% received cryoprecipitate, 69% received plasma, and 27% received
platelets. Patients who received any PRBCs had more than a twofold increase in nosocomial
infections (odds ratio, 2.15; 95% confidence interval, 1.01–4.58; p = 0.047). The number of
PRBCs given was also associated with the development of nosocomial infection (odds ratio, 1.10;
95% confidence interval, 1.05–1.16; p < 0.001).

CONCLUSION: Trauma patients in the PAMPer trial who received a transfusion of at least 1 U
of PRBCs incurred a twofold increased risk of nosocomial infection, and the risk of infection was
dose dependent.
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LEVEL OF EVIDENCE: Therapeutic/care management, level IV.

Keywords
Trauma; prehospital; resuscitation; blood; infection

Trauma is a leading cause of mortality before the age of 65 years in the United
States, and uncontrolled hemorrhage is one of the prevailing causes of preventable early

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death.1,2 Historical resuscitation strategies using crystalloid infusions are associated with
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worsening inflammation, resulting in worsening coagulopathy. Ratio-based damage-control

resuscitation using blood-component therapy mitigates the acute coagulopathy of trauma
present in a third of trauma patients upon admission.3-5 This strategy aids patients at
risk of hemorrhagic shock by decreasing endothelial permeability, restoring intravascular
volume, and preserving oxygen-carrying capacity.5,6 Early transfusion at the trauma center
is associated with a significant reduction in mortality in hypotensive trauma patients.2,6,7

Infection is one of the leading causes of mortality in trauma patients who survive at
least 3 days after the injury. Between 10% and 15% of trauma patients who survive at
least 48 hours after the initial insult develop infections, and in one study, nearly all blunt
trauma patients who died more than 7 days after their injuries died from sepsis.1,8-10 Blood
transfusions are associated with immunomodulatory effects including decreased immune
cell proliferation, release of proinflammatory cytokines, and delayed neutrophil apoptosis.
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Stored blood primes neutrophils for enhanced cytotoxicity, leading to a dose-dependent

response between the immunomodulatory effects and the amount of time a unit of blood was
stored.11-13 Recently, a large data analysis from the Trauma Quality Improvement Program
found a dose-dependent increase in infectious complications in trauma patients receiving
blood transfusions.14

The Prehospital Air Medical Plasma (PAMPer) trial demonstrated a 9.8% reduction in
absolute 30-day mortality for trauma patients at risk for hemorrhagic shock who were
treated with thawed plasma during air transport to a trauma center compared with those
treated with local standard protocol.5,15 The objective of our analysis was to characterize
the relationship between transfusion of blood products and the development of nosocomial
infections in the first 30 days among trauma patients enrolled in the PAMPer trial. We
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hypothesized that transfusion would be associated with a dose dependent development of

infections.

PATIENTS AND METHODS

Study Design and Patient Population
We performed a secondary analysis of patients enrolled in the PAMPer trial, a pragmatic,
multicenter, randomized, phase 3 trial involving trauma patients at risk of hemorrhagic
shock during air medical transport to a trauma center. Patients who were transported from
the scene of injury or from a referring emergency department to a participating trauma
center, with hypotension (systolic blood pressure of less than 90 mm Hg) and tachycardia
(heart rate greater than 108 beats per minute), or severe hypotension (systolic blood pressure
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of less than 70 mm Hg), at any time before arrival to the trauma center were eligible for
enrollment. Patients younger than 18 years or older than 90 years were excluded, along with
those who had an isolated fall from standing, documented spinal cord injury, penetrating
traumatic brain injury, traumatic cardiac arrest longer than 5 minutes, isolated hanging or
drowning, or severe (>20% total body surface area) burns. Pregnant patients and prisoners
were also excluded.

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Cluster randomization was used to assign enrolled patients into plasma or standard care
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groups. Patients in the plasma group received 2 U of either group AB or group A with a low
anti-B antibody titer (<1:100) thawed plasma by the air transport team. After administration
of 2 U of thawed plasma, resuscitation was continued according to standard protocols using
crystalloids and/or universal donor red blood cells (RBCs). Patients in the standard care
group received crystalloids and/or universal donor RBCs. No other aspects of treatment by
transport or trauma teams were altered. The institutional review boards at each participating
trauma center, including our local institutional board, approved the study design and also
provided exception from informed consent.5

Data Collected
All data were obtained as part of the PAMPer trial. Demographics data included age, sex,
race, ethnicity, height, and weight. Body mass index was calculated using available data for
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height and weight. Injury characteristics included mechanism of injury and injury to specific
body regions, Abbreviated Injury Scale scores, and Injury Severity Score (ISS). We recorded
blood product transfusion in the prehospital and in-hospital setting in the first 24 hours
after enrollment. The type and volume of blood product transfused in units were noted. All
surgical and interventional radiological interventions in the first 24 hours after enrollment
were recorded. Outcomes data included hospital length of stay (LOS), intensive care unit
(ICU) LOS, ventilator days, and in-hospital mortality.

Rate and type of infections among patients enrolled in the trial were obtained. Infectious
complications were collected for the PAMPer trial as bloodstream infections (catheter
related or not catheter related), ventilator-associated pneumonia, urinary tract infection, or
other. Infections were collected prospectively in the original study as one of the secondary
outcomes. In the original trial, nosocomial infections were monitored until postinjury day 30
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or until discharge from the intensive care unit and were based upon positive culture evidence
during the hospital admission. Diagnosis of a pneumonia required a positive culture of
more than 104 colony-forming units per milliliter from bronchoalveolar culture specimens
in addition to standard clinical and radiologic criteria. Bloodstream infections required
positive peripheral cultures. Urinary tract infections required more than 105 organisms/mL
of urine. For the purpose of our secondary analysis, all types of infectious complications
were grouped together.

Statistical Analysis
Because nosocomial infections are unlikely to develop in the first 72 hours after
hospitalization, we excluded patients with hospital LOS of less than 3 days. Descriptive
analysis was performed for the remaining patients to identify overall demographics, injury
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characteristics, incidence and volume of blood transfusions, and outcomes. These patients
were stratified into two groups: those with development of nosocomial infection and those
without nosocomial infection. Bivariate analysis was performed to identify differences in
demographics, injury characteristics, blood transfusions, and outcomes between the two
groups. Data are presented as median (interquartile range [IQR]) or frequency (n, %).
Categorical variables were analyzed using the χ2 or Fisher’s exact test, as appropriate.
Continuous variables were analyzed using the Mann-Whitney U test.

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To analyze whether blood transfusion was associated with infection, we performed two
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regression models. The first model used blood components as a binary categorical variables
(blood was given vs. no blood was given) to determine whether the presence of any
transfusion was associated with infection. This first multivariate regression model was
generated using age, sex, ISS, and use of any blood product transfusion to identify
the association between transfusion of blood products and development of nosocomial
infections. This model allows examination of added risk of infection when any blood is
given.

To identify whether a dose-dependent relationship exists, we performed a second

multivariable logistic regression model using number of transfused blood units in the
model. This second model use age, sex, ISS, and number of blood product components,
in number of units transfused, to determine the association with infection. This model allows
examination of the added risk of infection for each additional unit provided.
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Statistical analysis was performed using Stata version 15 (StataCorp, College Station, TX).
A two-tailed p value of less than 0.05 was considered significant.

RESULTS
A total of 501 patients, who were transported from 27 air medical bases to 9 participating
trauma centers, were analyzed in the PAMPer trial. Of these, 102 patients (20.4%) had
hospital LOS of less than 72 hours and were excluded from this secondary analysis (Fig.
1). For the remaining 399 patients (79.6%): median age was 45.5 years (IQR, 29.0–59.0
years), median body mass index was 28.4 kg/m2 (IQR, 24.3–32.4 kg/m2), 290 (72.9%) were
male, 346 (88.5%) were White, and 356 (96.7%) were non-Hispanic. The most common
mechanism of injury was blunt trauma (318 patients, 79.7%); 74 (18.5%) had penetrating
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mechanism, and 7 (1.8%) had both a blunt and penetrating mechanism. Median ISS was 22
(IQR, 12–29). Median hospital LOS was 13.0 days (IQR, 7.0–24.0 days), median ICU LOS
was 6.0 days (IQR, 2.0–14.0 days), and median ventilator days was 3.0 days (IQR, 1.0–10.0
days). In-patient mortality was 10.0% (40 patients).

The majority (307, 76.9%) of the patients received a packed red blood cell (PRBC)
transfusion within 24 hours of enrollment; 274 patients (68.7%) received plasma, either
prehospital or in-hospital; 108 patients (27.1%) received platelets, and 48 patients (12.0%)
received cryoprecipitate. Median volume of PRBC transfused was 3 U (IQR, 1–7 U), and
median volume of plasma transfused was 2 U (IQR, 0–4 U).

Infection data were available for 348 (87.2%), which showed an incidence of nosocomial
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infection of 26.7% (93 patients); 67 (19.3%) had pneumonia, 14 (4.0%) had bloodstream
infection, 10 (2.9%) had catheter-associated urinary tract infection, 8 (2.3%) had skin and
soft tissue infection, 7 (2.0%) had Clostridium difficile infection, 6 (1.7%) had empyema,
and 3 (0.9%) had complicated intra-abdominal infection; 255 patients (73.3%) did not have
a nosocomial infection.

Bivariate comparison between patients with and without nosocomial infections is shown
in Table 1. Patients who developed nosocomial infections were older (51 vs. 44 years,

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p = 0.040), more likely to be male (80% vs. 68%, p = 0.033), and more likely to have
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sustained a blunt mechanism of injury (93% vs. 78%, p = 0.004). Median ISS was higher
in patients who developed nosocomial infections (27 vs. 19, p < 0.001), along with a
higher incidence of traumatic brain injury, chest injury, and abdominal injury (all, p < 0.01).
Both groups underwent similar interventions; however, greater number of patients in the
nosocomial infection group received platelets (37% vs. 24%, p = 0.015), PRBCs (89% vs.
73%, p = 0.001), and cryoprecipitate (22% vs. 9%, p = 0.001) in first 24 hours, compared
with patients without nosocomial infections. Median units of fresh frozen plasma, platelets,
PRBCs, and cryoprecipitate transfused were also higher for the nosocomial infections group
(all, p < 0.01). This group had a higher hospital LOS (26 vs. 9 days, p < 0.001), higher ICU
LOS (17 vs. 4 days, p < 0.001), and more ventilator days (13 vs. 2 days, p < 0.001), without
a statistically significant difference in mortality (11% vs. 9%, p = 0.625).

A logistic regression model using age, sex, ISS, and blood products transfused identified
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age, male sex, ISS, transfusion of PRBCs, and transfusion of cryoprecipitate as independent
risk factors for nosocomial infections (all, p < 0.05; Table 2). A second model using age,
sex, ISS, and volume of blood products transfused showed age, male sex, ISS, and units of
PRBCs transfused as independent risk factors for nosocomial infections (all, p < 0.05; Table
3).

DISCUSSION
This secondary analysis of data obtained in the multicenter randomized prospective PAMPer
trial confirms an association between the transfusion of PRBCs in trauma patients at risk for
hemorrhagic shock and the development of nosocomial infections during the first 30 days of
hospitalization. A dose-dependent relationship was identified between the number of units of
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PRBCs received and the subsequent development of an infection.

This association has been demonstrated in other studies. Claridge et al.9 conducted a
secondary analysis of prospectively collected data for trauma patients that found an infection
rate of 33.0% in patients who received a transfusion compared with 7.6% in patients
who did not receive a transfusion. The authors found that PRBC transfusion was the only
independent predictor of a hospital-acquired infection. Similar to our results, this study
found a dose-dependent relationship between number of units or PRBCs and the incidence
of infection. Moore et al.13 conducted a similar analysis of a prospective database of
high-risk trauma patients. This group documented a linear association between the units
of blood transfused in the first 12 hours and the incidence of multisystem organ failure.13
Most recently, Nederpelt et al.14 performed analysis of data from the Trauma Quality
Improvement Program, which demonstrated an increased odds of infectious complications
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in a dose-dependent fashion using a multivariable logistic regression model. Our study

continues to confirm these findings using a dataset obtained through rigorous collection
methods in a prospective randomized trial.

Mounting evidence suggests that sepsis is likely secondary to early severe systemic
inflammatory response syndrome (SIRS) that results either from an initial ischemic insult
or from a trauma that primes the immune system resulting in a mild SIRS that is then

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compounded by other immunomodulatory insults such as blood transfusion. Trauma alone

induces immunosuppression through the immediate release of anti-inflammatory cytokines.1
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In another study that compared the effect of hemorrhage-induced immunosuppression with

that of a sepsis challenge, the mortality rate of mice was twofold higher in the hemorrhage
group.16 Although these effects are difficult to separate, transfusion has been shown to
confer up to a sixfold increased risk of developing SIRS.12 During storage of PRBCs,
proinflammatory molecules and cytokines from activated leukocytes are released and
subsequently found at higher concentrations in trauma patients who received a transfusion.12
Transfusions have been shown to activate both the coagulation and complement cascades,
increase numbers of suppressor cells, and compound the damage to underlying tissue10,17
By amplifying the existing immune system derangements of trauma patients, blood
transfusion upregulates the response to injury and renders the host more susceptible to
sepsis.10
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This secondary analysis of high-quality data at multiple high-volume trauma centers

raises two important possibilities. First, if providers have a higher index of suspicion for
nosocomial infections in patients who received larger volume of RBC, they may be more
inclined to test and treat at an earlier stage of disease. Second, providers may be inclined
to resuscitate with blood products besides PRBCs. Our findings further emphasize that
early hemorrhage control is paramount to not only the immediate but also the long-term
survival of the trauma patient. Post hoc analyses of the PAMPer trial5 and the Control of
Major Bleeding Trauma (COMBAT)18 trials also suggest that specific patient populations
may benefit the most from administration of early plasma, such as patients with long
transfer times and19 traumatic brain injury,20 and patients who receive less than 10 U of
PRBCs,4 suggesting that RBCs may be able to be spared and infections avoided, in certain
populations of trauma patients.
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In our analysis, there was no association between prehospital plasma transfusion and
infections, although the administration of plasma as the randomized intervention was likely
to bias this analysis toward the null. Our data suggest that damage-control resuscitation
that relies more heavily on plasma than PRBCs may decrease sepsis. The combination of
plasma and PRBCs has a greater reduction on mortality than either plasma alone, PRBCs
alone, or crystalloid.15 Multiple studies have also demonstrated decreased mortality with
higher ratios of plasma or platelets to prehospital PRBCs compared with balanced blood
product ratios.2,3,6 Additional analyses showed that administration of these higher ratios
administered within the first 6 hours resulted in lower total volumes of transfusions, likely
because of the early correction of the coagulopathy of trauma, mitigation of endothelial
injury, and reduction of crystalloid volume.21
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There are several limitations to this study. First, while the data come from a multicenter
randomized trial, this is a secondary observational analysis. While the original trial design
included collected data about prehospital transfusion of all types of blood products, which
lent itself to our inquiry, the data recorded were not specifically powered to characterize
the differences we have outlined. In addition, because infectious outcomes were not the
primary endpoint of the original study, the data collected for this outcome are likely to
be less robustly defined and consistent between centers. Differences exist in the baseline

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characteristics of each group so that we can only declare there to be an association between
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PRBC prehospital transfusions and infection rather than a true causality due to possible
confounders. For example, if hypotension increases the risk of infection, transfusion volume
may be a proxy for severity of hypotension; unfortunately, our analysis cannot differentiate
between these risks. We controlled for confounders in our analysis when possible, but our
results should promote other rigorous explorations of this relationship. Finally, like other
research that analyzed transfusions and infections, our study cannot measure the contribution
of immunomodulatory impacts of hemorrhage on infection as separate from the effects of
blood transfusion on infection.

In conclusion, transfusion of PRBCs is associated with an increased risk of the development

of nosocomial infections in trauma patients. There was a dose-dependent increase in the risk
of infection with each unit of PRBCs administered. These results have relevance in both
the prehospital and hospital setting. Providers should maintain a high index of suspicion
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for infection in patients who received large volumes of PRBCs. It will be important for us
to continue to monitor the effect of changing resuscitation strategies and the effect on the
development of subsequent infectious complications.

ACKNOWLEDGMENTS
We thank all PAMPer study collaborators, prehospital providers, site personnel, and research staff who were
essential for the collection of data for the PAMPer study.

This publication was made possible by the National Institutes of Health’s grant support to V.P.H. and the
Department of Defense’s grant support to J.L.S. for the PAMPer trial. Its contents are solely the responsibility of
the authors and do not necessarily represent the official views of the National Institutes of Health or the Department
of Defense.
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DISCLOSURE
V. P. H. is supported by the Clinical and Translational Science Collaborative of Cleveland (KL2TR002547) from the
National Center for Advancing Translational Sciences component of the National Institutes of Health and National
Institutes of Health roadmap for Medical Research. V. P. H.’s spouse is a consultant for Zimmer Biomet, Medtronic,
Sig Medical, and Atricure. The rest of the authors declare no conflicts of interest.

The original PAMPer trial was funded by a grant (W81XWH-12-2-0023) from the US Army Medical Research
and Material Command. The US Army and the Department of Defense had no role in the design and conduct of
the study, data collection and analysis, or the preparation of the article. No funding was received to perform this
secondary analysis.

REFERENCES
1. Claridge JA, Crabtree TD, Pelletier SJ, Butler K, Sawyer RG, Young JS. Persistent occult
hypoperfusion is associated with a significant increase in infection rate andmortality in major
trauma patients. J Trauma. 2000;48(1):8–14. [PubMed: 10647559]
Author Manuscript

2. Holcomb JB, del Junco DJ, Fox EE, et al. The Prospective, Observational, Multicenter, Major
Trauma Transfusion (PROMMTT) study: comparative effectiveness of a time-varying treatment
with competing risks. JAMA Surg. 2013;148(2):127–136. [PubMed: 23560283]
3. Zink KA, Sambasivan CN, Holcomb JB, Chisholm G, Schreiber MA. A high ratio of plasma and
platelets to packed red blood cells in the first 6 hours of massive transfusion improves outcomes in a
large multicenter study. Am J Surg. 2009;197(5):565–570. [PubMed: 19393349]
4. Anto VP, Guyette FX, Brown J, et al. Severity of hemorrhage and the survival benefit associated
with plasma: results from a randomized prehospital plasma trial. J Trauma Acute Care Surg.
2020;88(1):141–147. [PubMed: 31688793]

J Trauma Acute Care Surg. Author manuscript; available in PMC 2022 August 01.
 Ladhani et al. Page 9

5. Sperry JL, Guyette FX, Brown JB, et al. Prehospital plasma during air medical transport in trauma
patients at risk for hemorrhagic shock. N Engl J Med. 2018;379(4):315–326. [PubMed: 30044935]
Author Manuscript

6. Holcomb JB, Tilley BC, Baraniuk S, et al. , PROPPR Study Group. Transfusion of plasma, platelets,
and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the
PROPPR randomized clinical trial. JAMA. 2015;313(5):471–482. [PubMed: 25647203]
7. Brown JB, Cohen MJ, Minei JP, et al. Pretrauma center red blood cell transfusion is associated
with reduced mortality and coagulopathy in severely injured patients with blunt trauma. Ann Surg.
2015;261(5):997–1005. [PubMed: 24670858]
8. Fabian TC, Hess MM, Croce MA, Wilson RS, Wilson SE, Charland SL, Rodman JH, Boucher
BA. Superiority of aztreonam/clindamycin compared with gentamicin/clindamycin in patients with
penetrating abdominal trauma. Am J Surg. 1994;167(3):291–296. [PubMed: 8160899]
9. Claridge JA, Sawyer RG, Schulman AM, McLemore EC, Young JS. Blood transfusions correlate
with infections in trauma patients in a dose-dependent manner. Am Surg. 2002;68(7):566–572.
[PubMed: 12132734]
10. Tyburski JG, Wilson RF, Warsow KM, McCreadie S. A trial of ciprofloxacin and metronidazole vs
gentamicin and metronidazole for penetrating abdominal trauma. Arch Surg. 1998;133(12):1289–
Author Manuscript

1296. [PubMed: 9865645]

11. Malone DL, Dunne J, Tracy JK, Putnam AT, Scalea TM, Napolitano LM. Blood transfusion,
independent of shock severity, is associated with worse outcome in trauma. J Trauma.
2003;52(5):898–905.
12. Dunne JR, Malone DL, Tracy JK, Napolitano LM. Allogenic blood transfusion in the first 24 hours
after trauma is associated with increased systemic inflammatory response syndrome (SIRS) and
death. Surg Infect (Larchmt). 2004;5(4):395–404. [PubMed: 15744131]
13. Moore FA, Moore EE, Sauaia A. Blood transfusion. An independent risk factor for postinjury
multiple organ failure. Arch Surg. 1997;132(6):621–624.
14. Nederpelt CJ, El Hechi M, Parks J, Fawley J, Mendoza AE, Saillant N, King DR, Fagenholz PJ,
Velmahos GC, Kaafarani HMA. The dose-dependent relationship between blood transfusions and
infections after trauma: a population-based study. J Trauma Acute Care Surg. 2020;89(1):51–57.
[PubMed: 32102046]
15. Guyette FX, Sperry JL, Peitzman AB, et al. Prehospital blood product and crystalloid resuscitation
in the severely injured patient: a secondary analysis of the prehospital air medical plasma trial.
Author Manuscript

Ann Surg. 2021;273(2):358–364. [PubMed: 30998533]

16. Landers DF, Hill GE, Wong KC, Fox IJ. Blood transfusion-induced immunomodulation. Anesth
Analg. 1996;82(1):187–204. [PubMed: 8712400]
17. van de Watering LM, Hermans J, Houbiers JGA, van den Broek PJ, Bouter H, Boer F, Harvey
MS, Huysmans HA, Brand A. Beneficial effects of leukocyte depletion of transfused blood on
postoperative complications in patients undergoing cardiac surgery: a randomized clinical trial.
Circulation. 1998;97(6):562–568. [PubMed: 9494026]
18. Moore HB, Moore EE, Chapman MP, et al. Plasma-first resuscitation to treat haemorrhagic
shock during emergency ground transportation in an urban area: a randomised trial. Lancet.
2018;392(10144):283–291. [PubMed: 30032977]
19. Pusateri AE, Moore EE, Moore HB, et al. Association of prehospital plasma transfusion with
survival in trauma patients with hemorrhagic shock when transport times are longer than
20 minutes: a post hoc analysis of the PAMPer and COMBAT clinical trials. JAMA Surg.
2020;155(2):e195085. [PubMed: 31851290]
Author Manuscript

20. Gruen DS, Guyette FX, Brown JB, et al. Association of prehospital plasma with survival in
patients with traumatic brain injury: a secondary analysis of the PAMPer cluster randomized
clinical trial. JAMA Netw Open. 2020;3(10):e2016869. [PubMed: 33057642]
21. Brown JB, Sperry JL, Fombona A, Billiar TR, Peitzman AB, Guyette FX. Pre-trauma center red
blood cell transfusion is associated with improved early outcomes in air medical trauma patients. J
Am Coll Surg. 2015;220(5):797–808. [PubMed: 25840537]

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Figure 1.
Patient selection for secondary analysis.
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TABLE 1.

Bivariate Comparison Between Patients With and Without Nosocomial Infections

Nosocomial Infection No Nosocomial Infection

(n = 93) (n = 255) p
Ladhani et al.

Age, median (range), y 51.0 (33.0–63.5) 44.0 (29.0–57.0) 0.040

Sex, n (%) 0.033
Male 74 (79.6) 173 (67.8)
Female 19 (20.4) 82 (32.2)
Race, n (%) 0.738
White 84 (92.3) 226 (89.7)
African American 5 (5.5) 17 (6.7)
Other 2 (2.2) 9 (3.6)
Ethnicity, n (%) 0.734
Hispanic 2 (2.2) 9 (3.8)
Non-Hispanic 87 (97.8) 225 (96.2)
BMI, median (range), kg/m2 28.5 (23.9–32.3) 28.4 (24.4–32.5) 0.675
Mechanism of injury, n (%) 0.004
Blunt 86 (92.5) 198 (77.6)
Penetrating 5 (5.4) 52 (20.4)
Both 2 (2.2) 5 (2.0)
Traumatic brain injury, n (%) 40 (43.0) 68 (26.7) 0.004
Chest injury, n (%) 80 (86.0) 155 (60.8) <0.001
Abdominal injury, n (%) 64 (68.8) 123 (48.2) 0.001
Extremity injury, n (%) 54 (58.1) 139 (54.5) 0.555

J Trauma Acute Care Surg. Author manuscript; available in PMC 2022 August 01.
Spinal cord injury, n (%) 11 (11.8) 14 (5.5) 0.043
AIS, median (range)
Head 2 (0–4) 0 (0–3) 0.002
Face 0 (0–1) 0 (0–1) 0.799
Chest 3 (2–3) 2 (0–3) 0.006
Abdomen 2 (0–3) 2 (0–2) 0.103
Extremity 2 (0–3) 2 (0–3) 0.063
External 1 (0–1 1 (0–1) 0.335
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Nosocomial Infection No Nosocomial Infection

(n = 93) (n = 255) p
Median ISS 27 (17–34) 19 (10–29) <0.001
Interventions within 24 h, n (%)
Thoracotomy 5 (7.8) 8 (5.3) 0.472
Ladhani et al.

Exploratory laparotomy 35 (54.7) 66 (43.4) 0.130

Craniotomy/craniectomy 4 (6.3) 9 (5.9) 1.000
Interventional radiology 5 (7.8) 19 (12.5) 0.317
Orthopedic 24 (37.5) 60 (39.5) 0.786
Other 18 (28.1) 32 (21.1) 0.260
Blood products given within 24 h, n (%)
FFP 71 (76.3) 167 (65.5) 0.054
Platelets 34 (36.6) 60 (23.5) 0.015
PRBCs 83 (89.2) 185 (72.5) 0.001
Cryoprecipitate 20 (21.5) 22 (8.6) 0.001
Volume of blood products given within 24 h, median (range), U
FFP 2 (1.5–6.5) 2 (0–3) 0.001
Platelets 0 (0–1) 0 (0–0) 0.011
PRBCs 5 (2–11) 2 (0–6) <0.001
Cryoprecipitate 0 (0–0) 0 (0–0) 0.001
Hospital LOS, median (range), d 25.5 (17–31) 9 (5–18) <0.001
ICU LOS, median (range), d 17 (11–23.5) 4 (2–9) <0.001
Ventilator days, median (range), d 13 (7–20) 2 (1–6) <0.001
In-hospital mortality, n (%) 10 (10.8) 23 (9.0) 0.625

AIS, Abbreviated Injury Scale; BMI, body mass index; FFP, fresh frozen plasma.

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TABLE 2.

Association Between Blood Product Transfusion and Nosocomial Infection

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OR SE p 95% CI
Age 1.022 0.021 0.005 1.007–1.037
Male sex 1.969 0.678 0.027 1.082–3.583
ISS 1.031 0.031 0.002 1.011–1.052
PRBC transfusion 2.149 0.765 0.047 1.009–4.576
Cryoprecipitate transfusion 2.035 0.710 0.046 1.013–4.088

CI, confidence interval; OR, odds ratio; SE, significant error.

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 Ladhani et al. Page 14

TABLE 3.

Association Between Volume of Transfusion and Nosocomial Infection

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OR SE p 95% CI
Age 1.025 0.025 0.001 1.010–1.041
Male sex 2.059 0.722 0.020 1.123–3.776
ISS 1.033 0.032 0.001 1.012–1.053
Platelet units 0.889 −0.118 0.202 0.742–1.065
PRBC units 1.104 0.099 <0.001 1.050–1.162

CI, confidence interval; OR, odds ratio; SE, significant error.

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J Trauma Acute Care Surg. Author manuscript; available in PMC 2022 August 01.