Utilizing four-factor prothrombin complex concentrate (4F-PCC) and tranexamic acid (TXA) concomitantly may theoretically elevate the risk of thromboembolism compared to either agent alone. Certain clinical situations arise where a patient may be a candidate for both TXA and 4F-PCC, such as trauma with major hemorrhage requiring anticoagulation reversal. In the absence of published literature, it is largely unknown whether coadministration of both agents increases the risk of thromboembolic events. The objective of this study was to explore safety outcomes of utilizing both 4F-PCC and TXA concomitantly in patients requiring emergent anticoagulation reversal due to a major hemorrhage. A single-center, retrospective chart review was conducted in adult patients who received 4F-PCC + TXA or 4F-PCC alone for emergent anticoagulation reversal of warfarin, apixaban, or rivaroxaban. The primary endpoint was the occurrence of thromboembolic events. The secondary endpoint was all-cause in-hospital mortality. Of the 110 patients included, 74 received 4F-PCC only and 36 patients received both 4F-PCC and TXA. The occurrence of thromboembolism was significantly higher in the 4F-PCC + TXA group compared to the 4F-PCC group (16.7% vs 2.7%; P = 0.0144). The incidence of all-cause in-hospital mortality was similar between groups [19.4% (4F-PCC + TXA) vs 10.8% (4F-PCC); P = 0.346]. The utilization of both 4F-PCC and TXA for patients with major hemorrhage requiring emergent anticoagulation reversal was associated with a significantly higher risk of thromboembolism than 4F-PCC alone. Clinicians should use caution when utilizing 4F-PCC and TXA concomitantly.
Limited data exist describing the optimal treatment of pericarditis after acute blunt or penetrating trauma. Treatment with high-dose nonsteroidal anti-inflammatory drugs (NSAID), colchicine, or corticosteroids may not be feasible due to concomitant injuries. This was a retrospective, single-center, descriptive case series at a large, academic, Level 1 Trauma Center over a 10-year period. Patients admitted to the trauma service with a diagnosis of pericarditis at any point during index admission were eligible for inclusion. Groups were defined as colchicine-based treatment (monotherapy or combination) and any therapy besides colchicine, including no medications (surgical). The primary endpoint was therapy escalation defined as treatment modification, chart note documenting therapy failure, rehospitalization, repeat pericardial surgical intervention, or documentation of recurrent pericarditis. Secondary outcomes were treatment intolerance documented in a chart note including gastrointestinal bleed (GIB) and acute kidney injury (AKI). Eleven patients with traumatic pericarditis were included. Four (36%) patients received colchicine-based therapy: monotherapy (2, [50%]) or combination with NSAID (2, [50%]). Seven (63%) patients received non-colchicine treatment: 2 (29%) NSAID alone; 5 (71%) surgical management without medication. There were no occurrences of therapy escalation in either group. Treatment intolerances occurred in 1 (25%; AKI) patient in the colchicine group and 3 (43%; AKI, 2 [29%], GIB, 1 [14%]) patients in the non-colchicine group. Pericarditis is a rare complication after trauma, and no patients in this case series demonstrated treatment escalation. Additional, larger sample studies are necessary to guide optimal treatment in this uncommon but important population.
Continuous renal replacement therapy (CRRT) provides renal support for unstable ICU patients but significantly alters drug concentrations. For patients on long-term antiepileptics such as lamotrigine, CRRT may increase risk for breakthrough seizures due to subtherapeutic levels. Conversely, CRRT may aid in lamotrigine overdose. While partial clearance of lamotrigine by intermittent hemodialysis has been reported, CRRT clearance is not well studied. This study determined lamotrigine extraction by CRRT in an ex vivo system. Medication was administered at two concentrations: one therapeutic and one supratherapeutic to closed-loop, blood-primed, ex vivo CRRT circuits. Drug concentrations were measured in plasma, hemofiltrate (effluent), and matching control samples at specific time points. For each time point, percent recovery of lamotrigine was calculated, and differences between CRRT circuits and controls were analyzed using two-sample t-tests. Plasma lamotrigine concentrations decreased rapidly, with 10% (n = 3, SD = 4%) and 17% (n = 2, SD = 3%) recovery at four hours for therapeutic and supratherapeutic doses, respectively. Although lower starting concentrations trended toward greater clearance, differences were not statistically significant ( P = .13). Control concentrations remained stable, with approximately 100% recovery. Lamotrigine concentrations were significantly affected by CRRT circuits. Patients receiving lamotrigine who require CRRT may need dosing adjustments to maintain clinical efficacy. Additionally, CRRT effectively clears lamotrigine, suggesting potential utility in overdose management.
Four-factor prothrombin concentrate complex (4F-PCC) may be used for significant bleeding following cardiac surgery but the optimal dosing has not been established. The purpose of this study was to compare two dosing strategies of 4F-PCC in cardiac surgery patients. This retrospective chart review evaluated 4F-PCC dosing of 25 units/kg compared to 12.5 units/kg in cardiac surgery patients following a protocol change for 4F-PCC dosing. The primary outcome was major bleeding, defined as the number of patients receiving ≥3 packed red blood cell (PRBC) transfusions within 24 h of 4F-PCC administration. Secondary outcomes included other surrogate markers for bleeding (eg, Use of other blood products and hemostatic agents), thrombotic events within 14 days of surgery, hospital length of stay, and all-cause mortality. A total of 42 patients were included (31 patients in the 25 units/kg group and 11 patients in the 12.5 units/kg group). There was no difference in the number of patients that received ≥3 PRBC transfusions between the two groups with 15 patients (47.4%) in 25 units/kg group and 3 patients (27.3%) in 12.5 units/kg ( P = .299). Additionally, no difference was observed in amount of additional hemostatic agents administered, hospital length of stay or mortality between the two groups. A higher rate of thromboembolic events was observed among patients receiving 25 units/kg vs 12.5 units/kg (22.6% vs 0%, P = .161). Reduced dosing of 4F-PCC from 25 units/kg to 12.5 units/kg following cardiac surgery resulted in no difference in clinical or effectiveness outcomes.
ChatGPT-4o, an advanced Artificial Intelligence based large language model, has demonstrated utility for providing medical information. Data regarding its accuracy and usefulness for hyperlipidemia pharmacotherapy are limited. Additionally, the clinical implications of variability in responses generated from simultaneous identical prompts across multiple sessions remains poorly understood. This research aimed to (1) assess accuracy, (2) evaluate usefulness, and (3) examine perceived impact variability of ChatGPT-4o generated responses to hyperlipidemia-related clinical questions. Five questions addressing hyperlipidemia management and patient counseling were developed. Responses to the questions were collected simultaneously from three independent ChatGPT-4o sessions initiated in separate, newly opened ChatGPT windows. A modified Delphi technique using clinical pharmacy faculty evaluated responses for accuracy, usefulness, and impact variability. Scores were evaluated using a 3-point Likert scale. After initial scoring, responses were collected, collated, and redistributed to faculty for review and optional revision. Final evaluations and consensus were facilitated by a moderator during a virtual panel. Consensus was reached for all responses. Evaluations of response accuracy ranged from poor to good, while usefulness ranged between somewhat useful and very useful. Impact variability ranged from none to high across responses, which faculty concluded could impact patient management. Response variability may have potential clinical implications; however, the present study evaluated expert-perceived potential impact rather than actual patient outcomes. Users should be aware concurrently generated ChatGPT responses can differ in accuracy and usefulness. Clinical judgment and patient-centered multidisciplinary collaboration remain essential. Future directions include using a larger data set to corroborate findings.
