Publications

BACKGROUND: Pain management is essential in trauma. Sufentanil is a potent sublingual opioid analgesic with no active metabolites and rapid onset relative to oral medications. We hypothesize that compared to standard care, Sufentanil reduces the verbally administered numerical pain scale (VNRS) at 30 minutes.

METHODS: We performed a prospective multicenter, open-label, randomized trial utilizing level-1 trauma centers from within the Linking Investigator in Trauma and Emergency Services (LITES) network. Participants were randomly assigned in a 1:1 ratio to either sublingual sufentanil or standard care. We enrolled 150 patients from July 2022 to January 2024. The study was approved by the human subjects research protection offices of the University of Pittsburgh and the Department of Defense. Subjects were eligible if they had a trauma evaluation, were 18 to 70, had a VNRS (0-100) score ≥50, and remained in the ED for at least 30 minutes. We excluded patients who were prisoners, pregnant, allergic to opioids, required airway management, body mass index (BMI) >40, significant respiratory depression, suspected gastrointestinal obstruction, or other contraindication to analgesics. The primary outcome was the VNRS for clinical pain measurement (0-100) at 30 minutes after treatment. Secondary outcomes included adverse events (hypoxia, hypotension, need for airway management) and the incidence of nausea/vomiting/headache/dizziness requiring treatment. We hypothesize that sublingual sufentanil as compared to emergency department standard care, will reduce the VNRS at 30 minutes.

RESULTS: The study population had a mean age of 48 years (standard deviation [SD] 15) and was 32% female. The mechanism of injury was mostly blunt (96%). The VNRS at 30 minutes was 67 (SD 25) for the entire cohort, 66 (SD 23) in the sufentanil group, and 68 (SD 27) in the standard care group ( P = .37). The Health care Professional Global Assessment (HPGA) at 30 minutes showed decreased pain scores in the standard care group compared to sufentanil, with standard care having more patients scored as good or excellent ( P = .009). There was no difference in the incidence of nausea, vomiting, headache, dizziness, hypoxia, hypotension, or need for an advanced airway.

CONCLUSIONS: In this cohort of trauma patients with moderate to severe pain, the VNRS at 30 minutes after administration of analgesics did not differ between sublingual sufentanil and standard care. Adverse events did not differ between the groups suggesting the sublingual sufentanil in this population.

ABSTRACT: The liver is the most commonly injured abdominal solid organ regardless of mechanism. The majority of liver injuries are grades I to III, with 12% to 20% as grades IV and V. In the hemodynamically stable patient or prompt responder to resuscitation, 85% to 90% of blunt liver injuries can be managed nonoperatively, regardless of the grade of injury. The promulgation of nonoperative management has resulted in decreased overall mortality for blunt liver injury. On the other hand, over the past 30 years, major advances in resuscitation science, intensive care, damage-control surgery, and nonoperative adjuncts have done little to reduce the operative morbidity and mortality of grades IV and V liver injuries. Angiography with embolization is often effective in stopping bleeding. However, angioembolization confers additional risk of complications (i.e., major hepatic necrosis and sepsis). This review will briefly present critical surgical anatomy and grading systems for liver trauma, followed by organ-specific diagnostic, resuscitation, and triage considerations. It will review important limitations, risk factors for failure, and complications associated with nonoperative management and angioembolization. This article presents operative techniques and pearls for surgical treatment of the most severe injuries, including adjuncts for hemorrhage control. Finally, we suggest the 6 Ps as an operative strategy for liver injury: Push-Pack-Pringle-Put Back-Phone-Pivot.

LEVEL OF EVIDENCE: Level III.

OBJECTIVE: Endovascular treatment of acute limb ischemia, primarily consisting of catheter-directed thrombolysis (CDT), has been shown to reduce mortality without affecting limb salvage. Percutaneous thrombectomy (PT) devices have expanded endovascular approaches while decreasing thrombolytic use. Although many advocate for an endovascular-first approach, it is unclear which patients would benefit most from each strategy.

METHODS: We included adults (18+) who underwent revascularization for infrainguinal acute limb ischemia (January 2016 to December 2023) at a multi-hospital health care system. We compared amputation and mortality after endovascular vs open approaches using logistic regression, Kaplan-Meier curves, and Cox regression.

RESULTS: We included 315 patients: 145 undergoing an endovascular-first strategy (89 CDT, 51 PT, 5 angioplasty/stent) and 170 undergoing open therapy (132 open thrombectomy, 38 bypass). Patients undergoing endovascular-first treatment were less ischemic, had more prior stenting, and more acute-on-chronic disease. Patients undergoing PT with suction devices were less likely to undergo overnight CDT compared with those with rheolytic devices (21% vs 67%; P = .004). There were no differences in 30-day amputation or mortality, but 30-day reintervention was increased in the endovascular group (adjusted odds ratio, 2.29; 95% confidence interval [CI], 1.06-4.91; P = .03). Three-year amputation rates were not significantly different on univariable or multivariable analysis when comparing the endovascular-first approach with open. PT alone trended toward increased amputation rates compared to open (adjusted hazard ratio [aHR], 1.96; 95% CI, 0.98-3.94; P = .058); however, this was mainly driven by the use of rheolytic devices with an amputation rate of 64% vs 8% in suction devices. Furthermore, those with embolic disease had significantly increased amputation rates (aHR, 2.92; 95% CI, 1.29-6.58; P = .01; Pinteraction = .02) with any endovascular-first strategy, when compared with open therapy. Endovascular-first patients had decreased mortality on univariable analysis (16% vs 37%; log-rank = .004) but not multivariable analysis (aHR, 0.60; 95% CI, 0.32-1.13; P = .12). When separated by endovascular modality, CDT had decreased mortality compared with open (aHR, 0.41; 95% CI, 0.18-0.93; P = .033), whereas PT did not (aHR, 1.05; 95% CI, 0.47-2.35; P = .91). Although effect of treatment modality on outcomes was not moderated by Rutherford classification, only 22 patients underwent endovascular-first treatment for Rutherford 2b ischemia.

CONCLUSIONS: Endovascular-first therapy had increased 3-year amputation in patients with embolic etiology of disease compared with open therapy. We also saw increased 30-day reintervention with endovascular-first therapy when compared with open therapy. CDT had decreased 3-year mortality when compared with open therapy. PT devices had mixed results, indicating that this is a technology in evolution. Newer PT devices are effective at reducing thrombolytic usage, and their amputation and mortality rates were similar to open therapy. An endovascular-first approach to Rutherford 2b ischemia needs further evaluation.

BACKGROUND: Optimal medical therapy (OMT) is a modifiable factor that decreases mortality and cardiovascular events in patients with severe peripheral arterial disease. We hypothesized that preintervention OMT would be associated with improved 1-year reintervention and major adverse limb event (MALE) rates after elective endovascular revascularization for intermittent claudication (IC).

METHODS: Using the Vascular Quality Initiative (2010-2020), we identified patients with IC undergoing elective endovascular, hybrid, and open surgical interventions. Preoperative antiplatelet, statin, and nonsmoking status defined OMT components and created three groups: complete (all components), partial (1-2 components), and no OMT. The primary outcome was 1-year reintervention. Secondary outcomes included MALE and factors associated with OMT usage. Multivariable logistic regression generated adjusted odds ratios (aOR).

RESULTS: There were 39,088 patients (14,907 [38.1%] complete, 22,054 [56.4%)] partial, 2127 [5.4%] no OMT) who met our criteria. Patients with any OMT were more frequently older with more cardiovascular diseases and diabetes (P < .0001). Patients without OMT were more likely to be Black or with Medicare or Medicaid (P < .05). Observed 1-year reintervention (5.3% complete OMT, 6.1% partial OMT, 8.3% no OMT; P < .001) and MALE (5.6% complete OMT, 6.3% partial OMT, 8.8% no OMT; P < .001) were decreased by partial or complete OMT compared with no OMT. Complete OMT significantly decreased the adjusted odds of reintervention and MALE by 28% (aOR, 0.72, 95% confidence interval [95% CI], 0.59-0.88) and 30% (aOR, 0.70; 95% CI, 0.58-0.85), respectively, compared with no OMT. Partial OMT decrease the adjusted odds of reintervention and MALE by 24% (aOR, 0.76; 95% CI, 0.63-0.92) and 26% (aOR, 0.74; 95% CI, 0.62-0.89), respectively.

CONCLUSIONS: Preintervention OMT is an underused, modifiable risk factor associated with improved 1-year reintervention and MALE. Vascular surgeons are uniquely positioned to initiate and maintain OMT in patients with IC before revascularization to optimize patient outcomes.

BACKGROUND: Portal venous system aneurysms (PVAs) are increasingly diagnosed on cross-sectional computed tomography imaging. However, the natural history of these aneurysms is poorly understood, and reports are limited to small case series.

METHODS: Terms relevant to PVAs were searched in radiology reports (2010-2022), with PVA presence confirmed by manual review. PVA were defined as a diameter greater than 1.5 cm in patients without cirrhosis and 1.9 cm in those with cirrhosis. Aneurysm growth was defined as greater than 20% increase in size, whereas aneurysm regression was defined as greater than 20% decrease in size. Patient demographics, comorbid conditions, and PVA outcomes were abstracted. Univariate statistics were used to compare groups.

RESULTS: Thirty-eight aneurysms with radiographic follow up were identified in 35 patients, involving the portal vein (n = 18; 47.4%), splenic vein (n = 10; 26.3%), superior mesenteric vein (n = 3; 7.9%), and portal confluence (n = 7; 18.4%). Although 12 (31.6%) were idiopathic, the remaining 26 (68.4%) were associated with portal hypertension (n = 20; 52.6%) and prior liver transplant (n = 4; 10.5%). The median growth was 0.2 cm (range, -2.6 to 2.4 cm) over median follow up over 5.0 years (range, 0.3-16.6 years). Five PVAs (13.2%) regressed and were largely idiopathic (80.0%; P = .03). Thirteen PVAs (34.2%) grew and were associated with portal hypertension (n = 11; 84.6%; P = .003) and thrombosis (n = 6; 46.2%; P = .05). Nine PVAs (23.7%) thrombosed, predominantly in males (n =7; 77.8%). The median growth was 1.0 cm (range, -0.7 to 1.9 cm). Three patients (33.3%) were symptomatic from PVA thrombosis including abdominal pain (n = 2; 22.2%), intestinal ischemia (n = 1; 11.1%), and variceal bleeding (n = 2; 22.2%). Four patients (44.4%) were treated with anticoagulation. No aneurysms ruptured. Of the 58 PVAs initially identified with and without radiographic follow up, five (8.6%) underwent intervention with a median diameter of 4.0 cm (range, 3.4-5 cm). Intervention included vein ligation (n = 1; 20.0%), aneurysmorrhaphy (n = 1; 20.0%), and aneurysmectomy (n = 3; 60.0%). There was one case of aneurysm recurrence 20 years following resection and one postoperative mortality.

CONCLUSIONS: Two-thirds of PVAs, including those with size greater than 3 cm, remain stable on surveillance. Although annual surveillance is initially recommended to confirm PVA stability, interval imaging can be subsequently extended given low growth rates. Over 20% of PVAs thrombosed, but none ruptured. Although we did not observe any cases of rupture, the devastating consequences of rupture necessitate consideration of surgical intervention for large symptomatic PVAs.

BACKGROUND: Variations in light exposure are associated with changes in inflammation and coagulation. The impact of light spectra on venous thrombosis (VT) and arterial thrombosis is largely unexplored.

OBJECTIVES: To investigate the impact of altering light spectrum on platelet function in thrombosis.

METHODS: Wild-type C57BL/6J mice were exposed to ambient (micewhite, 400 lux), blue (miceblue, 442 nm, 1400 lux), or red light (micered, 617 nm, 1400 lux) with 12:12 hour light:dark cycle for 72 hours. After 72 hours of light exposure, platelet aggregation, activation, transcriptomic, and metabolomic changes were measured. The ability of released products of platelet activation to induce thrombosis-generating neutrophil extracellular trap formation was quantified. Subsequent thrombosis was measured using murine models of VT and stroke. To translate our findings to human patients, light-filtering cataract patients were evaluated over an 8-year period for rate of venous thromboembolism with multivariable logistic regression clustered by hospital.

RESULTS: Exposure to long-wavelength red light resulted in reduced platelet aggregation and activation. RNA-seq analysis demonstrated no significant transcriptomic changes between micered and micewhite. However, there were global metabolomic changes in platelets from micered compared with micewhite. Releasate from activated platelets resulted in reduced neutrophil extracellular trap formation. Micered also had reduced VT weight and brain infarct size following stroke. On subgroup analysis of cataract patients, patients with a history of cancer had a lower lifetime risk of venous thromboembolism after implantation with lenses that filter low-wavelength light.

CONCLUSION: Light therapy may be a promising approach to thrombus prophylaxis by specifically targeting the intersection between innate immune function and coagulation.

Hemostatic resuscitation is an essential aspect of treating traumatic bleeding. Trauma-induced coagulopathy is a multifactorial disorder that can lead to increased transfusion requirements. However, little is known about the interplay between coagulopathies and stored blood products used for hemostatic resuscitation, which themselves acquire dysfunction in the form of a storage lesion. Physiologically relevant models can aid in the study of trauma and hemostatic resuscitation by incorporating important aspects such as biological surfaces and flow regimes that mimic injury. This study aims to evaluate the contribution of platelet products under varying storage conditions in coagulopathic states. This study utilized microfluidic platforms of high shear, a flow regime relevant to injury, including a stenotic straight channel and a severe transected vessel injury device. Apheresis platelet products were collected from healthy volunteers, stored at room temperature (RT) or cold-stored (CS) (1°C-6°C), and tested for product cell count and intrinsic product function in a high-shear stenotic microfluidic device across storage days (D2, D5, and D7 for RT; D2, D5, D7, D14, and D21 for CS). Hemostatic resuscitation efficacy of products was assessed using induced coagulopathy models of dilution and thrombocytopenia (TP). In vitro hemostatic resuscitation was assessed in both the stenotic straight channel for kinetic platelet contributions and the transected-vessel injury device, using blood loss and clot composition as endpoints. CS products conserved inherent function despite decreasing platelet counts through storage D7. When mixed with coagulopathic blood, D2 RT products did not show hemostatic benefit in the dilutional coagulopathy (DC) model. However, both D2 RT and CS showed hemostatic benefits in the thrombocytopenia model. CS products (D5 and D7) also showed an enhanced ability to recruit recipient platelets in the thrombocytopenia model compared to RT. Overall, this study highlights disparate responses associated with product storage duration and temperature, indicating the need to further evaluate hemostatic resuscitation efficacy under flow in pathologically relevant models to guide transfusion practices.

INTRODUCTION: Traumatic brain injury (TBI) patients on antiplatelet therapy face higher mortality because of impaired platelet function, which may be treated by platelet transfusion. The value of testing platelet function in this cohort remains controversial. We aimed to evaluate the relationship between platelet function assays and outcomes in TBI patients on antiplatelet therapy receiving platelet transfusions. We hypothesized that the magnitude of change in platelet assay performance following a transfusion would predict meaningful clinical outcomes.

METHODS: A cohort of patients, aged 18 to 89 years, with a history of preinjury antiplatelet therapy or who required platelet transfusion, and who were deemed at risk for neurosurgical intervention, was selected from a prospective randomized controlled trial of platelet transfusion for TBI. Pre- and posttransfusion blood samples were drawn. Platelet hemostatic function assays (PHFAs) included thromboelastography with platelet mapping (TEG-PM) and VerifyNow. Logistic regression models assessed the association of temporal assay results with 30-day all-cause mortality, need for craniotomy, and initial and follow-up Rotterdam scores.

RESULTS: Data from 94 TBI patients (43% female) with a median age of 76 years were analyzed. The 30-day mortality rate was 14%. VerifyNow aspirin assay was able to capture increases in platelet function following a platelet transfusion in patients on aspirin (significant positive Δ = 65 aspirin response units, p < 0.001). Thromboelastography with platelet mapping parameters detected improved platelet function following transfusion, although the absolute value of changes was minimal. Thromboelastography with platelet mapping parameters predicted important clinical outcomes on logistic regression, although no significant associations with clinical outcomes were identified by the change in PHFA after transfusion or after adjusting for multiple comparisons.

CONCLUSION: Higher absolute pre- and posttransfusion values of TEG-PM were associated with decreased mortality, decreased need for neurosurgical intervention, and decreased risk of progression of hemorrhage in TBI patients taking antiplatelet agents, although neither the change in TEG-PM after transfusion nor any other PHFA value predicted outcomes.

LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level II.

OBJECTIVE: To determine the feasibility, efficacy, and safety of cold storage compared with room temperature (RT) platelet transfusion in patients with traumatic brain injury (TBI).

BACKGROUND: Data demonstrating the safety and efficacy of cold-stored platelet (CSP) transfusion are lacking after TBI.

METHODS: A phase 2, randomized, open-label clinical trial was performed at a single U.S. trauma center. Traumatic brain-injured patients with positive brain imaging and a need for platelet transfusion received up to 2 apheresis units of CSPs stored out to 14 days versus standard care RT platelet transfusion. The primary outcome was feasibility and the principal clinical outcome for efficacy and safety was the 6-month Glasgow Coma Scale-extended score.

RESULTS: The 6-month Glasgow Outcome Scale-extended score distributions were not different across cold stored and RT platelet arms (odds ratio: 1.58, 95% CI: 0.71 to 3.54, P = 0.27). A lower rate of neurosurgical craniotomy/craniectomy was found for those receiving CSPs (difference: -14.4%, 95% CI: -26.5% to -2.3%, P = 0.03). Adverse event rates did not differ across groups. The storage age of the cold-stored product was not associated with outcome differences.

CONCLUSIONS: In brain-injured patients requiring platelet transfusion, early CSP transfusion is feasible and did not result in improved 6-month Glasgow Coma Scale-extended scores. Early CSP transfusion was associated with a lower rate of neurosurgical operative intervention without an increase in adverse events. The storage age of the CSP product was not associated with outcome differences. Future phase 3 clinical trials are required to determine clinical outcome differences and safety attributable to CSP transfusion after TBI.

INTRODUCTION: Traumatic brain injury (TBI) patients on antiplatelet therapy face higher mortality because of impaired platelet function, which may be treated by platelet transfusion. The value of testing platelet function in this cohort remains controversial. We aimed to evaluate the relationship between platelet function assays and outcomes in TBI patients on antiplatelet therapy receiving platelet transfusions. We hypothesized that the magnitude of change in platelet assay performance following a transfusion would predict meaningful clinical outcomes.

METHODS: A cohort of patients, aged 18 to 89 years, with a history of preinjury antiplatelet therapy or who required platelet transfusion, and who were deemed at risk for neurosurgical intervention, was selected from a prospective randomized controlled trial of platelet transfusion for TBI. Pre- and posttransfusion blood samples were drawn. Platelet hemostatic function assays (PHFAs) included thromboelastography with platelet mapping (TEG-PM) and VerifyNow. Logistic regression models assessed the association of temporal assay results with 30-day all-cause mortality, need for craniotomy, and initial and follow-up Rotterdam scores.

RESULTS: Data from 94 TBI patients (43% female) with a median age of 76 years were analyzed. The 30-day mortality rate was 14%. VerifyNow aspirin assay was able to capture increases in platelet function following a platelet transfusion in patients on aspirin (significant positive Δ = 65 aspirin response units, p < 0.001). Thromboelastography with platelet mapping parameters detected improved platelet function following transfusion, although the absolute value of changes was minimal. Thromboelastography with platelet mapping parameters predicted important clinical outcomes on logistic regression, although no significant associations with clinical outcomes were identified by the change in PHFA after transfusion or after adjusting for multiple comparisons.

CONCLUSION: Higher absolute pre- and posttransfusion values of TEG-PM were associated with decreased mortality, decreased need for neurosurgical intervention, and decreased risk of progression of hemorrhage in TBI patients taking antiplatelet agents, although neither the change in TEG-PM after transfusion nor any other PHFA value predicted outcomes.

LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level II.