We performed a secondary analysis of harmonized data derived from the Prehospital Air Medical Plasma (PAMPer) Trial and Study of Tranexamic Acid during Air and Ground Medical Prehospital Transport (STAAMP) Trial.
The PAMPer Trial (NCT01818427) was a multicenter, prehospital, cluster-randomized trial that compared outcomes in injured patients at risk of hemorrhagic shock who received thawed plasma versus standard-care resuscitation during air medical transport from 2014 through 2017. Patients were eligible for enrollment if they had at least one episode of hypotension (systolic blood pressure < 90 mmHg) and tachycardia (heart rate > 108 beats per minute), or if they had any severe hypotension (systolic blood pressure < 70 mmHg) either before arrival of air medical transport or any time before arrival at the participating trauma center4.
The STAAMP Trial (NCT02086500) was a double-blinded, multicenter, prehospital, randomized trial in which differing doses of tranexamic acid (TXA) versus placebo were administered in the prehospital setting to patients at risk of hemorrhage from 2015 to 2019. Patients were eligible for inclusion if they experienced at least 1 episode of hypotension (systolic blood pressure < 90 mmHg) or tachycardia (heart rate > 110 beats per minute) before arrival at the participating center5.
Both studies employed exception from informed consent (EFIC) enrollment, after a period of community consultation and public notification. Patients were excluded if they were younger than 18 years of age or older than 90 years of age, intravenous or intraosseous access could not be established, had an isolated fall from standing, had a cervical cord injury, were a known prisoner or were pregnant, had a traumatic cardiac arrest that lasted longer than 5 min, had a penetrating brain injury, had injury due to isolated drowning or hanging, had isolated burns, or were admitted as an inpatient to an outside hospital.
PAMPer (STUDY20070132) and STAAMP trials ((STUDY19060072) were both approved by the University of Pittsburgh Institutional Review Board and at all other study sites. Informed consent was obtained from all subjects enrolled in each of the trials. All study methods were carried out in accordance with relevant guidelines and regulations.
Study population
Inclusion criteria for this secondary study were patients who were enrolled in the PAMPer trial (501 patients) and the STAAMP trial (903 patients), who survived beyond the first 24 hours post-injury, and who required at least one day of ICU-level care. These criteria were used to eliminate those patients enrolled in either of the trials who were too severely injured and suffered mortality before MOF or NI could develop or who were not severely injured and at lower risk of hemorrhagic shock, MOF, and NI.
Definitions
Day 0 was considered day of admission. NI was defined as positive culture evidence beyond the day of admission. If patients developed multiple nosocomial infections, the first diagnosed NI was used to calculate time to infection and for descriptive characteristics. Multiorgan failure was defined by the Denver Multiple Organ Dysfunction scoring system. The Denver criteria assigns scores to cardiac, respiratory, renal, and hepatic dysfunction and defines multiple organ failure as two or more organ systems failing (resulting in a score > 3) at least 48 h after significant injury13,17. Procedures required in the first 24 hours post-injury were analyzed and were specifically defined as operative interventions performed in the operating room. Resource utilization refers to use of hospital resources, including mechanical ventilators and respiratory support staff, hospital bed, food, nursing support, medication needs, laboratory and imaging needs during an ICU or hospital stay, procedures undergone, and resources needed for safe discharge—including rehabilitation and skilled nursing needs. In this study, resource utilization was measured using parameters such as having had a procedure in the first 24 hours, mechanical ventilation days, ICU length of stay, hospital length of stay, and discharge disposition. Thirty-day outcomes were missing for six patients who were alive at discharge prior to 30 days; for this study, in-hospital mortality was used as a proxy for 30-day mortality for those six patients.
Statistical analysis
The PAMPer and STAAMP databases were first combined and harmonized. Patients who died within 24 hours of injury and patients who spent less than one day in the intensive care unit were excluded from further analysis. Patients were stratified by development of MOF only, NI only, both MOF and NI, or neither ICU complication. Patient demographics, injury characteristics, and outcomes of patients who developed MOF and/or NI versus those who had an uncomplicated ICU course were compared. Timing of these ICU complications relative to hospital admission and mortality was characterized via Kaplan–Meier survival analyses. Patients who developed MOF were further stratified by diagnosis of early (≤ 3 days) versus late MOF (> 3 days)13 to compare time-dependent risk factors and outcomes. Chi-square was used for categorical variables, and independent-samples Mann–Whitney U Tests was used for continuous variables. Binary logistic regression was used to characterize independent mortality risk associated with MOF and NI, after adjusting for covariates, including patient demographics, injury severity, and prehospital trial enrollment. Finally, hospital resource utilization attributable to MOF and NI, including mechanical ventilation days, ICU and hospital length of stay, and post-discharge rehabilitation requirements, was evaluated. A p-value of ≤ 0.05 was considered significant for all analyses. Data was stored and analyzed using SPSS Statistics, version 27, for Mac (IBM, Armonk, NY).
Ethical approval and consent to participate
PAMPer (STUDY20070132) and STAAMP trials ((STUDY19060072) were both approved by the University of Pittsburgh Institutional Review Board and at all other study sites.
Conference presentation
Presented at Academic Surgical Congress, Orlando, Florida, February 2022.