Clinical outcomes for patients on antiplatelet and anticoagulants in thoracoabdominal trauma.

Introduction: Trauma outcomes can be greatly affected by antiplatelet and anticoagulant (AP/AC) use. The goal of this study was to compare outcomes in trauma patients on AP/AC undergoing emergent surgery for thoracoabdominal trauma at 35 level 1 and 2 trauma centers from 2014 to 2021. Methods: This was a retrospective cohort study of 2460 adult patients with a chest, abdomen, or pelvis abbreviated injury score (AIS) of 2 or more who underwent surgery within 24 h of admission. These patients were segregated into four main cohorts based on antiplatelet/anticoagulation use: those not on AP/AC, those taking direct-acting oral anticoagulants (DOACs), those taking clopidogrel, and those taking warfarin. Patients were excluded if they had surgery >24 h after presentation, were dead on arrival, or had any other body system AIS score of 3 or higher. Results: The mean injury severity score (ISS) in all four groups ranged from 16.3 to 18.6 (p = 0.834) with a mean time to operating room from 208 to 478 min (p < 0.001). Laparotomy was performed in 60 to 71 % (p > 0.01) of patients, regardless of AP/AC status, and thoracic procedures were performed in 3.1 to 9.3 % (p = 0.42) of patients. In-hospital mortality and hospice rates were highest in the clopidogrel group at 21.9 %, followed by warfarin at 13 %, DOACs at 15 %, and no AP/AC at 7.63 % (p = 0.008). Serious complications occurred in 61 % of patients on warfarin, 50 % of those on DOACs, and 44 % of those on clopidogrel. All of these groups demonstrated significantly higher complication rates than patients in the no AP/AC control group at 25 % (p < 0.001). Total transfusion of packed red blood cells and fresh frozen plasma did not differ significantly between the groups; however, 24-h platelet transfusion did. Patients on clopidogrel received 14 packs of platelets, while those on warfarin and DOACs received 8 and 13 packs respectively (p = 0.011). Patients on warfarin had the longest hospital length of stay (LOS) at 13 days and ICU LOS at 9 days, compared to those on DOACs (8 and 4), those on clopidogrel (7 and 3), and those not taking AC/AP (7 and 4) (hospital LOS p = 0.03, ICU LOS p = 0.019). Those on AC/AP were also noted to be significantly older than those on neither, with those taking these medications averaging out to be approximately 69 years old and those not on these medications averaging 37 years old (p < 0.001). Conclusion: There was significantly higher mortality in patients on clopidogrel and increased length of stay and risk of serious complications in patients taking DOACs and warfarin. In patients on AP/AC there was also a significantly longer time to surgery than in those not taking either. Given these associations trauma surgeons should consider intervening sooner on patients taking AP/AC on admission, as the delay to intervention may contribute to the risks for trauma patients and result in worse outcomes as well as higher rates of mortality.

Effects of Early Chemoprophylaxis in Traumatic Brain Injury and Risk of Venous Thromboembolism.

BACKGROUND: The optimal timing to initiate venous thromboembolism (VTE) prophylaxis in patients with a traumatic brain injury (TBI) is still unknown. We designed a study to determine the effect that timing of initiation of VTE prophylaxis has on VTE rates in TBI patients. METHODS: Patient records were obtained from 32 level 1 and 2 trauma centers in the Michigan Trauma Quality Improvement Program from 2008 to 2018. Overall, 5589 patients with a TBI were included and split into cohorts based on VTE prophylaxis initiation time. Outcomes included rate of VTE, mortality, and serious in-hospital complications. RESULTS: There were nine patients (1.3%) in the <24 hour group with a VTE as compared to 36 (2.6%) in the 24-48 hour group, 51 (4.1%) in the 48-72 hour group, and 181 (8.1%) in the >72 hour group (P < .001). The adjusted odds of VTE were significantly greater in patients initiated within 48-72 hours (AOR 2.861, 95% CI 1.271-6.439) and >72 hours (AOR 3.963, 95% CI 1.824-8.612) compared to <24 hours. Patients that received VTE prophylaxis within 24 hours had similar rates of serious in-hospital complication as patients initiated within 24-48 hours (AOR .956, 95% CI .637-1.434) and 48-72 hour (AOR 1.132, 95% CI .757-1.692) but less than the >72 hour group (AOR 1.662, 95% CI 1.154-2.393) groups. DISCUSSION: Patients initiated on VTE prophylaxis within 48 hours of presentation had lower incidence of VTE without a significant increase in serious complications.

The Effect of Antiplatelet Agents on Thromboelastography.

BACKGROUND: Thomboelastography (TEG) is a point of care viscoelastic test that provides an assessment of clot formation and kinetics. Antiplatelet agents are commonly used but there is limited literature evaluating their possible effects on overall clot kinetics. We aimed to evaluate the relationship between antiplatelet agents and clot kinetics as defined by TEG. METHODS: This is a retrospective study of adult patients who underwent TEG from February 2018 to July 2020. Patients who received anticoagulants or blood transfusions within 72 hours, had an incomplete TEG, were diagnosed with COVID-19, or had liver failure were excluded. Patients were stratified based on antiplatelet status. RESULTS: Of 1060 patients, 119 were included (50 controls, 69 antiplatelet agents-37 aspirin monotherapy, 26 dual antiplatelet therapy). Between the control and antiplatelet therapy groups, there was no significant difference in clot time, maximal clot strength, or fibrinogen level. When compared to control patients, patients on dual antiplatelets had significantly higher fibrinogen levels (408.1 mg/dL vs 481.5 mg/dL, P = .013) but no significant differences in clot time or maximal clot strength. In our subgroup analysis, patients on dual antiplatelets had increased maximal clot strength (58.8° vs 63°, P = .005) and fibrinogen levels (384.1 mg/dL vs 481.5 mg/dL, P = .005) compared to those on aspirin alone. DISCUSSION: Compared to control patients and those on aspirin alone, patients on dual antiplatelets have increased maximal clot strength and increased fibrinogen levels. These results can help physicians better target product resuscitation in patients who are on antiplatelet agents.

The Effect of Direct Oral Anticoagulants on Outcomes After Urgent or Emergent Cardiac Surgery.

OBJECTIVE: To determine the safety of performing urgent or emergent cardiac surgery within 5 days of a patient taking a direct oral anticoagulant (DOAC). DESIGN: A multicenter retrospective registry study. SETTING: Thirty-three hospitals in a quality collaborative from 2017 to 2019. PARTICIPANTS: Patients were included if they underwent urgent or emergent coronary artery bypass grafting (CABG). Patients were excluded if they received any anticoagulant or antiplatelet agent besides DOACs, heparin, or aspirin. INTERVENTIONS: Patients were stratified based upon the receipt of a DOAC within 5 days of their surgery. Patient cohorts included DOAC within 2 days, DOAC within 3-to-5 days, and no anticoagulation. Data were unavailable on the specific DOAC agent taken prior to admission. MEASUREMENTS AND MAIN RESULTS: There were 7,201 patients included, with 94 on DOACs. Intraoperative blood transfusion was required in 23.9% of patients on no anticoagulant, 26.2% on a DOAC within 3-to-5 days of surgery (odds ratio [OR] 0.98; 95% CI 0.46-2.11), and 30.3% on a DOAC within 2 days (OR 0.99; 95% CI 0.37-2.67). Five or more intraoperative blood products were required in 4.4% on no anticoagulant, 1.7% on DOAC within 3-to-5 days (OR 0.33; 95% CI 0.04-2.71), and 6.1% on DOAC within 2 days (OR 0.47; 95% CI 0.06-4.05). No difference in mortality was observed among the 3 groups (2.9% v 3.3% v 3.0%; p = 0.67). CONCLUSIONS: For urgent or emergent CABGs, no significant differences in minor bleeding, major bleeding, or mortality were observed in patients taking a DOAC within 5 days of surgery. This study was hypothesis-generating for performing urgent or emergent surgery sooner than 5 days after holding DOACs.

Blood Pressure Control in Acute Stroke: Labetalol or Nicardipine?

PURPOSE: To assess the safety and efficacy of continuous infusion (CIV)-labetalol compared to -nicardipine in controlling blood pressure (BP) in the acute stroke setting. MATERIALS: Patients were eligible if they had a diagnosis of an acute stroke and were administered either CIV-labetalol or CIV-nicardipine. Study outcomes were assessed within the first 24 h of the antihypertensive infusion. RESULTS: A total of 3,093 patients were included with 3,008 patients in the CIV-nicardipine group and 85 in the CIV-labetalol group. No significant difference was observed in percent time at goal BP between the nicardipine (82%) and labetalol (85%) groups (p = 0.351). There was also no difference in BP variability between nicardipine (37%) and labetalol (39%) groups (p = 0.433). Labetalol was found to have a shorter time to goal BP as compared to nicardipine (24 min vs. 40 min; p = 0.021). While CIV-nicardipine did have a higher incidence of tachycardia compared to labetalol (17% vs. 4%; p <0.001), the incidence of hypotension (13% vs. 15%; p = 0.620) and bradycardia (24% vs. 22%; p = 0.797) were similar. CONCLUSIONS: These results indicate that CIV-labetalol and CIV-nicardipine are comparable in safety and efficacy in controlling BP for patients with acute stroke.

Association of timing of initiation of pharmacologic venous thromboembolism prophylaxis with outcomes in trauma patients.

BACKGROUND: Patients are at a high risk for developing venous thromboembolism (VTE) following traumatic injury. We examined the relationship between timing of initiation of pharmacologic prophylaxis with VTE complications. METHODS: Trauma quality collaborative data from 34 American College of Surgeons Committee on Trauma-verified levels I and II trauma centers were analyzed. Patients were excluded if they were on anticoagulant therapy at the time of injury, had hospitalization <48 hours, or received no or nonstandard pharmacologic VTE prophylaxis (heparin drip). Patient comparison groups were based on timing of initiation of VTE prophylaxis relative to hospital presentation (0 to <24 hours, 24 to <48 hours, ≥48 hours). Risk-adjusted rates of VTE events were calculated accounting for patient factors including type of pharmacologic agent in addition to standard trauma patient confounders. A sensitivity analysis was performed excluding patients who received blood in the first 4 hours and/or patients with a significant traumatic brain injury. RESULTS: Within the 79,386 patients analyzed, there were 1,495 (1.9%) who experienced a VTE complication and 1,437 (1.8%) who died. After adjusting for type of prophylaxis and patient factors, the risk of a VTE event was significantly increased in the 24- to <48-hour (odds ratio, 1.26; 95% confidence interval, 1.09-1.47; p = 0.002) and ≥48-hour (odds ratio, 2.35; 95% confidence interval, 2.04-2.70; p < 0.001) cohorts relative to patients initiated at 0 to <24 hours. These VTE event findings remained significant after exclusion of perceived higher-risk patients in a sensitivity analysis. CONCLUSION: Early initiation of pharmacologic VTE prophylaxis in stable trauma patients is associated with lower rates of VTE. LEVEL OF EVIDENCE: Diagnostic, level III.

Early Chemoprophylaxis in Severely Injured Trauma Patients Reduces Risk of Venous Thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) remains a serious complication for trauma patients. While early VTE prophylaxis has gained traction, the timing of prophylaxis remains uncertain. We hypothesized that VTE prophylaxis within 24 hours of admission would have lower VTE rates and similar rates of adverse events in seriously injured patients. METHODS: Trauma patients were included from 32 American College of Surgeons verified Level 1 and 2 trauma centers over a 10-year period. Patients with injury severity score (ISS) <15, death or discharge within 48 hours of arrival, or who received no prophylaxis were excluded. RESULTS: 14 096 patients received VTE prophylaxis with an ISS of ≥15. Patients given prophylaxis at <24 hours had fewer VTE events and trended toward fewer serious in-hospital complications. Mortality and return to the operating room were similar across groups. Hospital and intensive care unit length of stay in the <24 hours prophylaxis group was significantly shorter when VTE prophylaxis was initiated earlier. CONCLUSIONS: In severely injured trauma patients with ISS >15, early VTE prophylaxis within 24 hours significantly reduced the risk of VTE as compared with delayed prophylaxis. Early chemoprophylaxis was found to be efficacious in reducing the incidence of VTE; however, the safety of this practice should be evaluated by future prospective studies.

Effect of Preinjury Oral Anticoagulants on Outcomes Following Traumatic Brain Injury from Falls in Older Adults.

BACKGROUND: Warfarin has been the oral anticoagulant of choice for the treatment of thromboembolic disease. However, upward of 50% of all new anticoagulant prescriptions are now for direct oral anticoagulants (DOAC). Despite this, outcome data evaluating preinjury anticoagulants remain scarce following traumatic brain injury (TBI). Our study objective is to determine the effects of preinjury anticoagulation on outcomes in older adults with TBI. METHODS: Patient data were obtained from 29 level 1 and 2 trauma centers from 2012 to June 30, 2018. Overall, 8312 patients who were aged 65 years or older, suffering a ground level fall, and with an Abbreviated Injury Scale (AIS) head score of ≥ 3 were identified. Patients were excluded if they presented with no signs of life or a traumatic mechanism besides ground level fall. Statistical comparisons were made using multivariable analyses with anticoagulant/antiplatelet use as the independent variable. RESULTS: Of the total patients with TBI, 3293 were on antiplatelet agents (AP), 669 on warfarin, 414 on warfarin + AP, 188 on DOACs, 116 on DOAC + AP, and 3632 on no anticoagulant. There were 185 (27.7%) patients on warfarin and 43 (22.9%) on a DOAC with a combined outcome of mortality or hospice as compared to 575 (15.8%) in the no anticoagulant group (p<0.001). After adjusting for patient factors, there was an increased risk of mortality or hospice in the warfarin (OR 1.60; 95% CI 1.27-2.01) and DOAC group (OR 1.67; 95% CI 1.07-2.59) as compared to no anticoagulant. Warfarin + AP was associated with an increased risk of mortality or hospice (OR 1.61; 95% CI 1.18-2.21) that was not seen with DOAC + AP (OR 0.93; 95% CI 0.46-1.87) as compared to no anticoagulant. CONCLUSIONS: In older adults with TBI, preinjury treatment with warfarin or DOACs resulted in an increased risk of mortality or hospice whereas preinjury AP therapy did not increase risk. Future studies are needed with larger sample sizes to directly compare TBI outcomes associated with preinjury warfarin versus DOAC use.

Perspectives from the frontline: A pharmacy department's response to the COVID-19 pandemic.

PURPOSE: The global coronavirus disease 2019 (COVID-19) pandemic has created unprecedented strains on healthcare systems around the world. Challenges surrounding an overwhelming influx of patients with COVID-19 and changes in care dynamics prompt the need for care models and processes that optimize care in this medically complex patient population. The purpose of this report is to describe our institution's strategy to deploy pharmacy resources and standardize pharmacy processes to optimize the management of patients with COVID-19. METHODS: This retrospective, descriptive report characterizes documented pharmacy interventions in the acute care of patients admitted for COVID-19 during the period April 1 to April 15, 2020. Patient monitoring, interprofessional communication, and intervention documentation by pharmacy staff was facilitated through the development of a COVID-19-specific care bundle integrated into the electronic medical record. RESULTS: A total of 1,572 pharmacist interventions were documented in 197 patients who received a total of 15,818 medication days of therapy during the study period. The average number of interventions per patient was 8. The most common interventions were regimen simplification (15.9%), timing and dosing adjustments (15.4%), and antimicrobial therapy and COVID-19 treatment adjustments (15.2%). Patients who were admitted to an intensive care unit care at any point during their hospital stay accounted for 66.7% of all interventions documented. CONCLUSION: A pharmacy department's response to the COVID-19 pandemic was optimized through standardized processes. Pharmacists intervened to address a wide scope of medication-related issues, likely contributing to improved management of COVID-19 patients. Results of our analysis demonstrate the vital role pharmacists play as members of multidisciplinary teams during times of crisis.

Association of mortality among trauma patients taking preinjury direct oral anticoagulants versus vitamin K antagonists.

BACKGROUND: The population of patients on anticoagulant or antiplatelet therapy for medical conditions is increasing. The objective of this study was to investigate the effects of preinjury anticoagulation or antiplatelet therapy on outcomes after trauma. METHODS: This cohort study analyzed data from the Michigan Trauma Quality Improvement Program from 2012 to 2017 and included trauma patients age ≥16 years with an Injury Severity Score ≥5 treated at 29 hospitals. The primary outcome was in-hospital mortality. RESULTS: Of 115,042 trauma patients, 44.2% were women and 78.2% were white with a mean age (standard deviation) of 59.1 (23.2) years. A total of 23,196 patients were on antiplatelet therapy, 3,855 on warfarin, 1,893 on warfarin + antiplatelet agent, 1,306 on a direct oral anticoagulant, and 717 patients on direct oral anticoagulant + antiplatelet therapy. We observed an increased risk of mortality in patients on preinjury antiplatelet (odds ratio [OR] 1.17; 95% confidence interval [CI] 1.02-1.33), warfarin (OR 1.32; 95% CI 1.05-1.65), or warfarin + antiplatelet therapy (OR 1.59; 95% CI 1.18-2.14). Patients on a direct oral anticoagulant only were not at statistically increased risk for mortality. CONCLUSION: Preinjury antiplatelet and/or warfarin use was associated with an increased risk of mortality after traumatic injury. Preinjury direct oral anticoagulant use was not associated with a statistically increased risk of adverse outcomes.

Safety of high-dose intravenous labetalol in hypertensive crisis.

PURPOSE: The study assesses the safety of high-dose intravenous (i.v.) labetalol in adults. METHODS: This is a retrospective administrative record review of 28 hospitals in one health care system, from October 2010 through October 2015. Patients were included if they received 300 mg of i.v. labetalol within a 24-hour period. Vital signs, adverse events and cumulative medication doses were obtained for up to 24 hours while on labetalol. Adverse events were defined as any systolic blood pressure measurement less than 90 mm Hg or heart rate less than 60 beats per minute. RESULTS: We analyzed the records of 188 patients who received i.v. labetalol at higher than the maximum recommended dose of 300 mg. The mean dose of labetalol was 996 mg (range 300 to 4465 mg). The cumulative labetalol dose was not associated with adverse safety outcomes (p = 0.428), although eighty-one patients (44.3%) experienced adverse events. Sixty-six patients (36.5%) developed bradycardia and 34 patients (18.6%) developed hypotension. Only five patients (2.7%) required a rescue agent for refractory adverse events. CONCLUSION: A retrospective review of high-dose i.v. labetalol hydrochloride with doses greater than 300 mg in 24 hours observed a high rate of bradycardia and hypotension, but the study found that these events rarely caused clinically significant hemodynamic compromise and was not statistically associated with adverse events.

Continuous-Infusion Labetalol vs Nicardipine for Hypertension Management in Stroke Patients.

BACKGROUND: Labetalol and nicardipine are antihypertensives commonly used in the management of elevated blood pressure (BP) following an acute stroke, but there is limited evidence to suggest which agent as a continuous infusion should be used preferentially in this setting. OBJECTIVE: This study aimed to compare the safety, efficacy, and ease of administration of continuous-infusion labetalol with continuous-infusion nicardipine following an acute stroke. METHODS: This retrospective cohort study of patients with acute ischemic stroke or intracerebral hemorrhage included patients if they received either study agent within 24 hours of admission. The primary outcome was percent time spent at goal BP. Secondary outcomes included time to goal BP, the number of dose adjustments, and use of rescue antihypertensives. RESULTS: The analysis included 99 patients who received labetalol- (n = 34) or nicardipine- (n = 65) continuous infusions. Intracerebral hemorrhage was the most common stroke subset (n = 81) followed by acute ischemic stroke (n = 18). There was no statistical difference in time at goal BP (labetalol 68.0%, nicardipine 67.0%; P = .885), rescue antihypertensive use (labetalol 14.7%, nicardipine 24.6%; P = .2570), time spent 10% above or below mean systolic BP (labetalol 35.5%, nicardipine 33.5%; P = .885), time to goal BP (labetalol 81.4 minutes, nicardipine 56.3 minutes; P = .162), and mean number of dose adjustments (labetalol 5.9, nicardipine 6.9; P = .262). CONCLUSIONS: Labetalol- and nicardipine-continuous infusions were comparable in the studied safety and efficacy outcomes including time at goal and BP variability. Further prospective studies are needed to validate these safety and efficacy findings and to assess clinical outcomes.