Navpreet K. Dhillon

Association Between Enoxaparin Dosage Adjusted by Anti-Factor Xa Trough Level and Clinically Evident Venous Thromboembolism After Trauma.

Importance Trauma patients are at high risk for developing venous thromboembolism (VTE). The VTE rate when enoxaparin sodium is dosed by anti-factor Xa (anti-Xa) trough level is not well described. Objective To determine whether targeting a prophylactic anti-Xa trough level by adjusting the enoxaparin dose would reduce the VTE rate in trauma patients. Design, Setting, and Participants Single-institution, historic vs prospective cohort comparison study at an urban, academic, level I trauma center. The prospective cohort was enrolled from August 2014 to May 2015 and compared with a historic cohort admitted from August 2013 to May 2014. Trauma patients who received enoxaparin adjusted by anti-Xa trough level (adjustment group) were compared with those who received enoxaparin sodium at a dosage of 30 mg twice daily (control group). Patients were excluded if they were younger than 18 years, had a length of hospital stay less than 2 days, or had preexisting deep vein thrombosis. Patients were excluded from the adjustment group for changes in the choice of thromboprophylaxis (heparin, enoxaparin once-daily dosing, early ambulation), hospital discharge before initial trough levels could be drawn, or incorrect timing of trough levels. Exposures Anti-Xa trough levels were monitored in patients in the adjustment group receiving 3 or more consecutive doses of enoxaparin sodium, 30 mg twice daily. Patients with a trough level of 0.1 IU/mL or lower received enoxaparin sodium increased by 10-mg increments. After providing 3 adjusted doses of enoxaparin, the trough level was redrawn and the dosage was adjusted as necessary. Patients in the control group received enoxaparin sodium at a dosage of 30 mg twice daily without adjustments. Main Outcomes and Measures Rates of symptomatic VTE (deep vein thrombosis and pulmonary embolism, confirmed by duplex ultrasonography and chest computed tomographic angiography, respectively) and bleeding risk. Results A total of 205 patients (mean [SD] age, 41.3 [18.2] years; 75.1% male) were studied, 87 in the adjustment group and 118 in the control group, with similar baseline characteristics and injury profiles. Subprophylactic anti-Xa troughs were noted in 73 of 87 patients (83.9%) in the adjustment group, and the majority of patients (57 of 87 patients [65.5%]) required dosage adjustment of enoxaparin sodium to 40 mg twice daily. Incidence of VTE was significantly lower in the adjustment group than in the control group (1.1% vs 7.6%, respectively; P = .046). When the adjustment group was compared with the control group, no significant difference was noted in the rate of packed red blood cell transfusion (6.9% vs 12.7%, respectively; P = .18) or mean (SD) hematocrit at discharge (34.5% [6.3%] vs 33.4% [6.8%], respectively [to convert to proportion of 1.0, multiply by 0.01]; P = .19). Conclusions and Relevance In this study, subprophylactic anti-Xa trough levels were common in trauma patients. Enoxaparin dosage adjustment may lead to a reduced rate of VTE without an increased risk of bleeding.

Analysis of Survival After Initiation of Continuous Renal Replacement Therapy in a Surgical Intensive Care Unit

Importance Continuous renal replacement therapy (CRRT) benefits patients with renal failure who are too hemodynamically unstable for intermittent hemodialysis. The duration of therapy beyond which continued use is futile, particularly in a population of patients admitted to and primarily cared for by a surgical service (hereinafter referred to as surgical patients), is unclear. Objective To analyze proportions of and independent risk factors for survival to discharge after initiation of CRRT among patients in a surgical intensive care unit (SICU). Design, Setting, and Participants This retrospective cohort study included all patients undergoing CRRT from July 1, 2012, through January 31, 2016, in an SICU of an urban tertiary medical center. The population included patients treated before or after general surgery and patients admitted to a surgical service during inpatient evaluation and care before liver transplant. The pretransplant population was censored from further survival analysis on receipt of a transplant. Exposures Continuous renal replacement therapy. Main Outcomes and Measures Hospital mortality among patients in an SICU after initiation of CRRT. Results Of 108 patients (64 men [59.3%] and 44 women [40.7%]; mean [SD] age, 62.0 [12.7] years) admitted to the SICU, 53 were in the general surgical group and 55 in the pretransplant group. Thirteen of the 22 patients in the pretransplant group who required 7 or more days of CRRT died (in-hospital mortality, 59.1%); among the 12 patients in the general surgery group who required 7 or more days of CRRT, 12 died (in-hospital mortality, 100%). In the general surgical group, each day of CRRT was associated with an increased adjusted odds ratio of death of 1.39 (95% CI, 1.01-1.90; P = .04). Conclusions and Relevance Continuous renal replacement therapy is valuable for surgical patients with an acute and correctable indication; however, survival decreases significantly with increasing duration of CRRT. Duration of CRRT does not correlate with survival among patients awaiting liver transplant.

Beta blockers in critically ill patients with traumatic brain injury: Results from a multicenter, prospective, observational American Association for the Surgery of Trauma study

BACKGROUND Beta blockers, a class of medications that inhibit endogenous catecholamines interaction with beta adrenergic receptors, are often administered to patients hospitalized after traumatic brain injury (TBI). We tested the hypothesis that beta blocker use after TBI is associated with lower mortality, and secondarily compared propranolol to other beta blockers. METHODS The American Association for the Surgery of Trauma Clinical Trial Group conducted a multi-institutional, prospective, observational trial in which adult TBI patients who required intensive care unit admission were compared based on beta blocker administration. RESULTS From January 2015 to January 2017, 2,252 patients were analyzed from 15 trauma centers in the United States and Canada with 49.7% receiving beta blockers. Most patients (56.3%) received the first beta blocker dose by hospital day 1. Those patients who received beta blockers were older (56.7 years vs. 48.6 years, p < 0.001) and had higher head Abbreviated Injury Scale scores (3.6 vs. 3.4, p < 0.001). Similarities were noted when comparing sex, admission hypotension, mean Injury Severity Score, and mean Glasgow Coma Scale. Unadjusted mortality was lower for patients receiving beta blockers (13.8% vs. 17.7%, p = 0.013). Multivariable regression determined that beta blockers were associated with lower mortality (adjusted odds ratio, 0.35; p < 0.001), and propranolol was superior to other beta blockers (adjusted odds ratio, 0.51, p = 0.010). A Cox-regression model using a time-dependent variable demonstrated a survival benefit for patients receiving beta blockers (adjusted hazard ratio, 0.42, p < 0.001) and propranolol was superior to other beta blockers (adjusted hazard ratio, 0.50, p = 0.003). CONCLUSION Administration of beta blockers after TBI was associated with improved survival, before and after adjusting for the more severe injuries observed in the treatment cohort. This study provides a robust evaluation of the effects of beta blockers on TBI outcomes that supports the initiation of a multi-institutional randomized control trial. LEVEL OF EVIDENCE Therapeutic/care management, level III.

Clinical correlates to assist with chronic traumatic encephalopathy diagnosis: Insights from a novel rodent repeat concussion model

INTRODUCTION Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to repetitive head injuries. Chronic traumatic encephalopathy symptoms include changes in mood, behavior, cognition, and motor function; however, CTE is currently diagnosed only postmortem. Using a rat model of recurrent traumatic brain injury (TBI), we demonstrate rodent deficits that predict the severity of CTE-like brain pathology. METHODS Bilateral, closed-skull, mild TBI was administered once per week to 35 wild-type rats; eight rats received two injuries (2×TBI), 27 rats received five injuries (5×TBI), and 13 rats were sham controls. To determine clinical correlates for CTE diagnosis, TBI rats were separated based on the severity of rotarod deficits and classified as “mild” or “severe” and further separated into “acute,” “short,” and “long” based on age at euthanasia (90, 144, and 235 days, respectively). Brain atrophy, phosphorylated tau, and inflammation were assessed. RESULTS All eight 2×TBI cases had mild rotarod deficiency, 11 5×TBI cases had mild deficiency, and 16 cases had severe deficiency. In one cohort of rats, tested at approximately 235 days of age, balance, rearing, and grip strength were significantly worse in the severe group relative to both sham and mild groups. At the acute time period, cortical thinning, phosphorylated tau, and inflammation were not observed in either TBI group, whereas corpus callosum thinning was observed in both TBI groups. At later time points, atrophy, tau pathology, and inflammation were increased in mild and severe TBI groups in the cortex and corpus callosum, relative to sham controls. These injury effects were exacerbated over time in the severe TBI group in the corpus callosum. CONCLUSIONS Our model of repeat mild TBI suggests that permanent deficits in specific motor function tests correlate with CTE-like brain pathology. Assessing balance and motor coordination over time may predict CTE diagnosis.

Decreased transport time to the surgical intensive care unit

INTRODUCTION Extended stay in the emergency department (ED) is associated with worse outcomes in critically ill trauma patients. We conducted a human factors analysis to better understand impediments for patient flow when a surgical ICU (SICU bed is available in order to reduce ED LOS. METHODS This is a retrospective review of all trauma patients admitted to a protected SICU through the ED during 2011 and 2014. In 2010, a 24-hour protected SICU bed protocol was implemented to make a bed readily available. During 2013 human factors analysis helped to describe flow disruptions; related interventions were introduced to facilitate rapid transport from the ED to SICU. The interventions required the following prior to CT scanning: immediate ICU bed orders placed by the ED physician and ED to ICU personnel communication. Direct transport from the CT scanner to the ICU was mandated. Data including patient demographics, injury severity, ED LOS, ICU LOS, and hospital LOS was collected and compared between 2011 (PRE) and 2014 (POST). RESULTS A total of 305 trauma patients admitted from the ED to the SICU were analyzed; 174 patients in 2011 (PRE) and 131 in 2014 (POST). Average age was 46 years and patients had a mean admission GCS and injury severity score (ISS) of 12.3 and 15.9, respectively. The cohorts were similar in age, mechanism of injury, initial vital signs, and injury severity. After implementing the human factors interventions, decreases were noted in the mean ED LOS (2.4 v. 3.0 hours, p=0.005) and ICU LOS (4.0 v. 4.8 days, p=0.023). No differences in hospital LOS or mortality were observed. CONCLUSIONS While an open SICU bed protocol may facilitate rapid transport of trauma patients from the ED to the ICU, additional human factors interventions emphasizing improved communication and coordination can further reduce time spent in the ED. LEVEL OF EVIDENCE Level IV, Economic/Decision.

What Happens After a Stop the Bleed Class? The Contrast Between Theory and Practice

OBJECTIVE The Department of Homeland Security launched the Stop the Bleed initiative, a campaign intended to teach bystanders hemorrhage control strategies. Despite the programs popularity, little is known about actions taken by participants afterwards. We sought to determine how often participants acquired the equipment that is necessary in applying the skills taught. DESIGN A standardized survey instrument was distributed to all American College of Surgeons Bleeding Control Basic (B-Con) class participants from 05/2017 to 01/2018. The instrument queried about the likelihood of applying skills and obtaining materials. A web-based survey was administered one month later inquiring whether materials were obtained and barriers that would prohibit acquisition. SETTING Academic, urban, Level I trauma center. PARTICIPANTS Healthcare and nonhealthcare personnel. RESULTS There were 336 and 183 participants who completed the initial and subsequent web-based survey, respectively. Participants indicated a high likelihood of applying a tourniquet (95.5%), applying pressure (97.9%), and packing a wound (96.4%), if required. Additionally, 74.7% and 76.2% reported a high likelihood of obtaining a tourniquet and packing material, respectively. However, only 21.3% and 50.8% obtained a tourniquet and packing material, respectively, 1 month later. Cost, time, and accessibility of items during a time of need were cited to be common reasons for not obtaining these materials. CONCLUSIONS Despite reporting a high likelihood of utilizing hemorrhage control skills upon completion of the B-Con class, few went on to acquire the materials needed to apply these skills among those who responded. These results may be impacted by loss of follow up and response bias. Developing strategies that allow for easy access to materials is imperative and may lead to both better implementation of the purposes of the program and improved dissemination of its principles within the community.

Trauma patients with lower extremity and pelvic fractures: Should anti-factor Xa trough level guide prophylactic enoxaparin dose?

BACKGROUND Adequate venous thromboembolism (VTE) prophylaxis is essential after trauma, especially in patients with lower extremity and/or pelvic fractures. We sought to investigate if prophylactic enoxaparin dosed by anti-Xa trough levels could reduce clinically evident VTE in trauma patients with lower extremity or pelvic injury. METHODS Prospective data was collected on trauma patients admitted for at least two days with any lower extremity and/or pelvic fracture and who received enoxaparin for VTE prophylaxis between October 2013 and January 2016. Patients in the control cohort received enoxaparin at 30 mg twice daily. Patients in the adjustment cohort had anti-Xa trough levels measured after three or more consecutive doses of enoxaparin. Those with a trough level of 0.1 IU/mL or lower had their dosage increased by 10-mg increments. RESULTS Of the 159 patients included, 58 (36.5%) were monitored with anti-Xa trough levels. The cohorts were similar in age, sex, regional AIS, ISS score, ICU and hospital length of stay, proportion of patients with diagnostic testing for VTE, and time to first enoxaparin dose. Initial enoxaparin dosing in the majority of patients (84.5%) who had anti-Xa trough levels measured was subprophylactic. Patients receiving enoxaparin dosed by anti-Xa trough level had a significantly lower VTE rate than those who did not (1.7% v. 13.9%, p = 0.03). CONCLUSIONS Prophylactic enoxaparin adjusted by anti-factor Xa level may lead to a decreased rate of clinically evident VTE among trauma patients with lower extremity and/or pelvic fractures. Our findings indicate that the initial dose of enoxaparin was frequently too low.

Patterns of Vasopressor Utilization During the Resuscitation of Massively Transfused Trauma Patients

BACKGROUND The use of vasopressors (VP) in the resuscitation of massively transfused trauma patients might be considered a marker of inadequate resuscitation. We sought to characterize the utilization of VP in patients receiving massive transfusion and examine the association of their use with mortality. METHODS Trauma patients admitted from January 2011 to October 2016 receiving massive transfusion, defined as 3 units of pRBC within the first hour from admission, were selected for analysis. Demographics, admission vital signs and labs, use of VP, surgical interventions and outcomes were collected. Standard statistical tools were utilized. RESULTS Over the 5-year study period, 120 trauma patients met inclusion criteria. The median age was 39 years with 77% being male and 41% sustaining a penetrating injury. Patients who received VP [VP (+)] were more likely to have a lower admission GCS (median 4.5 vs. 14.0, p <0.01) and less likely to have a penetrating injury (31% vs. 54%, p=0.02). The overall mortality was 49% and significantly higher in the VP (+) cohort (60% vs. 34%, AHR: 9.9, adjusted p=0.03). Mortality increased in a stepwise fashion with increasing number of VP utilized, starting at 34% for no VP, to 78% for 3 VP, and 100% for 5 or more. The majority of deaths in the VP (-) group (88%) occurred within one day from admission. For the VP (+) group, 57% of deaths occurred within one day, with the remaining 43% occurring at a later time. CONCLUSION In the era of massive transfusion protocols, vasopressors are commonly utilized in exsanguinating trauma patients and their use is associated with a higher mortality risk. Deaths in patients receiving vasopressors are more likely to occur later compared to those in patients who do not receive vasopressors. Further research to characterize the role of these agents in the resuscitation of trauma patients is required.

The risk of delayed intracranial hemorrhage with direct acting oral anticoagulants after trauma: A two-center study

BACKGROUND The aim of this study was to characterize the risk of a delayed intracranial hemorrhage (ICH) in trauma patients on direct-acting oral anticoagulants (DOACs). METHODS Patients on DOACs admitted to two Level I Trauma Centers between 2014 and 2017 were reviewed. Only patients with a negative admission CT brain were included. The primary outcome was a delayed ICH. RESULTS Overall, 249 patients were included. The median age was 81 years with 82% undergoing a repeat CT. Three patients developed a delayed ICH (1.2%). One developed an ICH after receiving tissue plasminogen activator for a cerebrovascular accident after two negative CTs. Excluding this patient, the incidence dropped to 0.8%. None required neurosurgical intervention. CONCLUSION For patients at risk for a TBI who are on DOACs, repeat cross-sectional imaging of the brain when the initial imaging is negative is not necessary. A period of clinical observation may be warranted.