Impact of Factor Xa Inhibitor Reversal with Prothrombin Complex Concentrate in Patients with Traumatic Brain Injuries.

BACKGROUND: Anticoagulant use prior to trauma has been associated with increased incidence of traumatic brain injury (TBI), intracranial hemorrhage (ICH) progression, and mortality. Prothrombin complex concentrates (PCCs) are commonly used as off-label treatments for factor Xa inhibitor-associated life-threatening hemorrhage. At this time, there is no consensus regarding appropriate indication, target dose, or outcomes of PCC administration in patients presenting with traumatic ICH. This study seeks to evaluate the impact of reversal with PCC on hemorrhage progression and outcomes in patients with TBI on preinjury factor Xa inhibitors. METHODS: This single-center retrospective cohort study included patients ≥ 18 years presenting with an acute TBI of any severity on apixaban or rivaroxaban from September 1, 2016, to September 1, 2019. Patients were grouped on the basis of receipt of PCCs for reversal (i.e., reversal or no reversal). Exclusion criteria included spontaneous ICH or known coagulopathy. Propensity score matching was conducted with the following variables: age, Abbreviated Injury Scale (head) score, and Charlson Comorbidity Index score. The primary outcome was hemorrhage stability within 48 h. Secondary outcomes included degree of hemorrhage progression, in-hospital mortality, discharge disposition, and incidence of thromboembolic events. RESULTS: Of the 115 patients meeting inclusion criteria, 84 were included in the propensity score matched data set. Baseline characteristics, comorbidities, and TBI severity were similar. The majority of patients in the reversal group (35 [83.3%]) and the no reversal (NR) group (40 [95.2%]) experienced a mild TBI (admission Glasgow Coma Scale score of 14 to 15). In the reversal group, patients received 34.3 units/kg activated PCC, 30.5 units/kg four-factor PCC, or 54.9 units/kg four-factor PCC and activated PCC on average. There was no difference observed in the incidence of hemorrhage progression (10.8% NR vs. 15.0% reversal; p = 0.739) or in median change in ICH volume (0 mL NR vs. 1 mL reversal; p = 0.2199) between groups. Additionally, reversal did not affect in-hospital mortality (3 [7.1%] NR vs. 4 [9.5%] reversal; p > 0.999). One patient in the reversal group developed a deep vein thrombosis (DVT) during the hospitalization; however, this did not result in a statistically significant difference in the occurrence of DVT (p > 0.999). CONCLUSIONS: This study demonstrated that PCC used for the treatment of factor Xa inhibitor-associated ICH related to mild TBI did not significantly impact the incidence or degree of hemorrhage progression, and PCC treatment did not result in increased thromboembolic events.

23.4% Sodium Chloride Versus Mannitol for the Reduction of Intracranial Pressure in Patients With Traumatic Brain Injury: A Single-Center Retrospective Cohort Study.

BACKGROUND: Intermittent doses of mannitol or hypertonic saline are recommended to treat elevated intracranial pressure (ICP). However, it is unclear if one agent is more effective than the other. Previous studies have compared mannitol and hypertonic saline in reduction of ICP, with conflicting results. However, no study thus far has compared 23.4% sodium chloride with mannitol. OBJECTIVE: The objective of this study was to determine the difference in absolute reduction of ICP 60 minutes after infusion of 23.4% sodium chloride versus mannitol. METHODS: This was a single-center retrospective cohort study that included patients at least 16 years old admitted to the trauma/surgical intensive care unit between August 8, 2016, and August 30, 2018, who received either 23.4% sodium chloride 30 mL and/or mannitol 0.5 g/kg and had an ICP monitor or external ventricular drain in place. The primary outcome was absolute reduction in ICP 60 minutes after infusion of hyperosmolar therapy. RESULTS: In all, 31 patients and 162 doses of hyperosmolar therapy were included in the analysis. There was no statistically significant difference in the primary end point of absolute reduction of ICP 60 minutes after infusion of hyperosmolar therapy comparing 23.4% sodium chloride 30 mL with 0.5 g/kg mannitol (P = 0.2929). There was no statistically significant difference found for any secondary end points. CONCLUSION AND RELEVANCE: No difference was found for absolute reduction of ICP at 30, 60, and 120 minutes, respectively, after infusion of hyperosmolar agent or time to next elevated ICP. Patient-specific parameters should be used to guide the choice of hyperosmolar agent to be administered.

Dexmedetomidine versus propofol for prolonged sedation in critically ill trauma and surgical patients.

BACKGROUND: and Purpose: Currently, dexmedetomidine versus propofol has primarily been studied in medical and cardiac surgery patients with outcomes indicating safe and effective sedation. The purpose of this study was to assess the efficacy of dexmedetomidine versus propofol for prolonged sedation in trauma and surgical patients. METHODS: This was a single-center prospective study conducted in the Trauma/Surgical Intensive Care Unit (ICU) at a Level I academic trauma center. It included patients 18 years of age or older requiring mechanical ventilation who were randomly assigned based on unit bed location to receive either dexmedetomidine or propofol. The primary outcome was duration of mechanical ventilation. Secondary outcomes included mortality; proportion of time in target sedation; incidence of delirium, hypotension, and bradycardia; and ICU and hospital length of stay (LOS). RESULTS: A total of 57 patients were included. Baseline characteristics were similar between groups. There was no significant difference in duration of mechanical ventilation (median [IQR]) between the dexmedetomidine (78.5[125] hours) and propofol (105[130] hours; p = 0.15) groups. There was no difference between groups in ICU mortality, ICU and hospital LOS, or incidence of delirium. Safety outcomes were also similar. Patients in the dexmedetomidine group spent a significantly greater percentage of time in target sedation (98[8] %) compared to propofol group (92[10] %; p = 0.02). CONCLUSIONS: Our results suggest that, similar to medical and cardiac surgery patients, dexmedetomidine and propofol are safe and effective sedation agents in critically ill trauma and surgical patients; however, dexmedetomidine achieves target sedation better than propofol for this specific population.

Quetiapine for delirium prophylaxis in high-risk critically ill patients.

BACKGROUND: Delirium is common in patients admitted to the surgical trauma intensive care unit (ICU), and the risk factors for these patients differ from medical patients. Given the morbidity and mortality associated with delirium, efforts to prevent it may improve patient outcomes, but previous efforts pharmacologically have been limited by side effects and insignificant results. We hypothesized that scheduled quetiapine could reduce the incidence of delirium in this population. METHODS: The study included 71 adult patients who were at high-risk for the development of delirium (PRE-DELIRIC Score ≥50%, history of dementia, alcohol misuse, or drug abuse). Patients were randomized to receive quetiapine 12.5 mg every 12 h for delirium or no pharmacologic prophylaxis within 48 h of admission to the ICU. The primary end point was the incidence of delirium during admission to the ICU. Secondary end points included time to onset of delirium, ICU and hospital length of stay (LOS), ICU and hospital mortality, duration of mechanical ventilation, and adverse events. RESULTS: The incidence of delirium during admission to the ICU was 45.5% (10/22) in the quetiapine group and 77.6% (38/49) in the group that did not receive pharmacological prophylaxis. The mean time to onset of delirium was 1.4 days for those who did not receive prophylaxis versus 2.5 days for those who did (p = 0.06). The quetiapine group significantly reduced ventilator duration from 8.2 days to 1.5 days (p = 0.002). CONCLUSIONS: The findings suggested that scheduled, low-dose quetiapine is effective in preventing delirium in high-risk, surgical trauma ICU patients.

Impact of Obesity on Warfarin Reversal With Fixed-Dose Factor VIII Inhibitor Bypassing Activity (aPCC).

BACKGROUND: Data are limited addressing anticoagulant reversal in obese patients using activated prothrombin complex concentrate (aPCC). OBJECTIVE: Assess the impact of obesity on INR reversal with fixed aPCC dosing. METHODS: Institutional review board-approved, retrospective cohort conducted in a large academic medical center. Patients 18 years or older who received fixed-dose aPCC for warfarin-associated hemorrhage were included. Patients who received aPCC for any other indications or who had no follow-up INR after aPCC administration were excluded. Patients with an INR of 5 or greater received 1000 units aPCC, whereas those with INR less than 5 received 500 units aPCC, per institutional protocol. Patients were stratified into obese and nonobese based on body mass index. Primary end point was INR reversal, defined as repeat INR of 1.4 or less within 4 hours following aPCC treatment, without a repeated dose. Secondary end points included percentage change in INR, proportion of patients requiring an additional dose of aPCC, bleeding complications, thrombotic complications, hospital length of stay, and in-hospital mortality. RESULTS: 259 patients were included, of whom 83 were obese (32%). A significantly higher proportion of nonobese patients achieved an INR of 1.4 or less within 4 hours of treatment (169 [96.02%] vs 69 [83.13%]; P = 0.0004). There were no differences in any secondary end points. CONCLUSION AND RELEVANCE: When fixed-dose aPCC is used for warfarin reversal, obesity is associated with a significantly lower rate of INR reversal, without increased bleeding. This study adds to the limited amount of literature on aPCC dosing in obesity.

Treatment With Oral Versus Intravenous Acetaminophen in Elderly Trauma Patients With Rib Fractures: A Prospective Randomized Trial.

BACKGROUND: Rib fractures are common injuries among traumatically injured patients, and elderly patients with rib fractures are at increased risk for adverse events and death. The purpose of this study was to determine if oral Per os (PO) acetaminophen is as effective as intravenous (IV) acetaminophen in treating the pain associated with rib fractures. METHODS: We performed a single-center, randomized, placebo-controlled, double-blinded study. Trauma patients who were ≥65 years old and had ≥1 rib fracture were included in this study. Patients were randomized into IV acetaminophen and oral placebo (n = 63) or IV placebo and oral solution acetaminophen (n = 75) groups. The primary outcome was a mean reduction in pain score at 24 hours, and secondary outcomes included opioid use, intensive care unit (ICU) length of stay (LOS), hospital LOS, hospital mortality, the difference in incentive spirometry, and development of pneumonia. RESULTS: Among the 138 patients included, there was no statistically significant difference between the 2 study groups in a mean reduction in pain score at 24 hours after injury (PO: 3.24, IV: 2.49; P = .230). Opioid pain medication use was equivalent between groups (P = .212), and there was no significant difference in hospital mortality rate between groups (P = .827). There was no statistically significant difference in ICU LOS, hospital LOS, or development of pneumonia. DISCUSSION: In elderly trauma patients (age ≥65 years) with 1 or more rib fractures, PO acetaminophen is equivalent to IV acetaminophen for pain control, with no difference in morbidity or mortality. Oral acetaminophen should be preferentially used over IV acetaminophen when treating the elderly trauma patient with rib fractures.

Nonsteroidal anti-inflammatory drugs' impact on nonunion and infection rates in long-bone fractures.

BACKGROUND: There is a dearth of clinical data regarding the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on long-bone fracture (LBF) healing in the acute trauma setting. The orthopedic community believes that the use of NSAIDs in the postoperative period will result in poor healing and increased infectious complications. We hypothesized that, first, NSAID use would not increase nonunion/malunion and infection rates after LBF. Second, we hypothesized that tobacco use would cause higher rates of these complications. METHODS: A retrospective study of all patients with femur, tibia, and/or humerus fractures between October 2009 and September 2011 at a Level 1 academic trauma center was performed . In addition to nonunion/malunion and infection rates, patient records were reviewed for demographic data, mechanism of fracture, type of fracture, tobacco use, Injury Severity Score (ISS), comorbidities, and medications given. RESULTS: During the 24-month period, 1,901 patients experienced LBF; 231 (12.1%) received NSAIDs; and 351 (18.4%) were smokers. The overall complication rate including nonunion/malunion and infection was 3.2% (60 patients). Logistic regression analysis with adjusted odds ratios were calculated on the risk of complications given NSAID use and/or smoking, and we found that a patient is significantly more likely to have a complication if he or she received an NSAID (odds ratio, 2.17; 95% confidence interval, 1.15-4.10; p < 0.016) in the inpatient postoperative setting. Likewise, smokers are significantly more likely to have complications (odds ratio, 3.19; 95% confidence interval, 1.84-5.53; p < 0.001). CONCLUSION: LBF patients who received NSAIDs in the postoperative period were twice as likely and smokers more than three times likely to suffer complications such as nonunion/malunion or infection. We recommend avoiding NSAID in traumatic LBF. LEVEL OF EVIDENCE: Epidemiologic & therapeutic study; level II.

Futility Assessment of Recombinant Factor VII Activated for the Treatment of Hemorrhagic Shock Requiring Massive Transfusion.

OBJECTIVE: Recombinant human factor VII activated (rFVIIa) is an adjuvant therapy in patients receiving massive transfusion for hemorrhagic shock. We compared patient characteristics and outcomes to determine futility criteria for the administration of rFVIIa in patients receiving massive transfusion for hemorrhagic shock. METHODS: This was a retrospective cohort analysis of patients who received both massive transfusion and rFVIIa. Consecutive trauma patients were allocated to 1 of 2 cohorts: survivors and nonsurvivors. RESULTS: Seventy-two subjects comprised the study: 27 were survivors and 45 were nonsurvivors. A univariate analysis revealed that nonsurvivors were older and had a more profound coagulopathy as measured by prothrombin time. A stepwise logistic regression revealed an increased odds of death in those patients who were older (odds ratio [OR], 1.048; 95% CI, 1.008 -1.091), had a higher admission prothrombin time (OR, 1.561; 95% CI, 1.152-2.116), and received more fresh frozen plasma (OR, 1.098; 95% CI 1.023-1.179). In addition we saw a protective effect with increased platelet administration (OR, 0.645; 95% CI, 0.446-0.932). CONCLUSION: The use of rFVIIa for massive transfusion in middle-aged patients with moderate coagulopathy experiencing hemorrhagic shock may be considered futile. However, if rFVIIa is to be used as part of a massive transfusion protocol, adequate administration of platelets should be ensured.

Indacaterol: a novel long-acting ß(2) -agonist.

Bronchodilator drugs are the foundation for the treatment of chronic obstructive pulmonary disease. The principal inhaled bronchodilator treatments used are ß(2) -agonists and anticholinergics, either alone or in combination. Currently available ß(2) -agonists are of either short duration and used multiple times/day, or of long duration, which requires twice-daily administration. Indacaterol is considered an ultra-long-acting ß(2) -agonist and was recently approved for use in the United States. Its duration of action is approximately 24 hours, allowing for once-daily administration. Cough was the most commonly reported adverse effect with use of indacaterol. Cough usually occurred within 15 seconds of inhalation of the drug, lasted around 6 seconds, was not associated with bronchospasm, and did not cause discontinuation of the drug. Otherwise, the drug's safety profile was similar to that of other bronchodilators. Based on similar improvement in spirometric measurements compared with other bronchodilator drugs and the convenience of its once-daily dosing, indacaterol may be beneficial in the management of mild-to-moderate chronic obstructive pulmonary disease, either alone or in combination with anticholinergic drugs administered once/day.

Use of inhaled epoprostenol in patients with H1N1 influenza-associated acute respiratory distress syndrome: a case series.

OBJECTIVE: To report a series of patients with confirmed novel influenza A (H1N1) and refractory hypoxemia secondary to acute respiratory distress syndrome (ARDS) treated with inhaled epoprostenol. CASE SUMMARY: Four patients admitted to our institution with confirmed H1N1 and refractory hypoxemia were treated with inhaled epoprostenol as potential salvage therapy. All patients were treated initially with antimicrobial agents, followed by oral oseltamivir at the time of suspicion or confirmation of H1N1. None of the patients received intravenous peramivir or extracorporeal membrane oxygenation. Clinically significant improvement in oxygenation was seen in only 1 of the patients receiving inhaled epoprostenol. Mortality was significant, with only 1 patient discharged from the hospital. DISCUSSION: Use of inhaled epoprostenol for the treatment of hypoxemia secondary to ARDS has been reported, with conflicting results. Deliveries via the inhalational route compared to the intravenous route theoretically preferentially vasodilate well-ventilated areas of the pulmonary vasculature, improving arterial oxygenation and pulmonary gas exchange. Increase in the ratio of arterial oxygen tension to fraction of inhaled oxygen is greatest upon initiation of inhaled epoprostenol, but this benefit has not been conclusively demonstrated to persist throughout therapy. Serious H1N1 presents a unique challenge for clinicians, often requiring the use of salvage therapies to treat critically ill patients. CONCLUSIONS: Given the variable response to treatment, it remains unclear whether inhaled epoprostenol is beneficial in H1N1-associated ARDS. Identification of patients for whom this therapy is most appropriate remains a clinical challenge.