Acute treatment of intracranial hemorrhage complicated by hemophilia a and emicizumab therapy.

Among patients with hemophilia A with or without FVIII inhibitors, emicizumab prophylaxis has demonstrated significantly reduced bleeding events. However, emicizumab interferes with clotting-based assays used for monitoring FVIII activity, resulting in falsely elevated FVIII activity. This lack of accurate monitoring can complicate the dosing of intravenous therapeutic FVIII clotting factor concentrates in the treatment of critical bleeding events. This case report aims to inform providers who frequently treat hemophilia-associated hemorrhages about emicizumab's effect on clotting-based assays essential for monitoring factor replacement.

Therapeutic Hypothermia Following Cardiopulmonary Arrest: A Systematic Review and Meta-Analysis with Trial Sequential Analysis.

Introduction: The risk-benefit profile of therapeutic hypothermia is controversial with several randomized controlled trials providing conflicting results. Aim of Study: The purpose of this systematic review and meta-analysis was to determine if therapeutic hypothermia provides beneficial neurologic outcomes relative to adverse effects. Material and Methods: MEDLINE and EMBASE databases were searched for randomized controlled trials of post-cardiac arrest patients comparing therapeutic hypothermia (~33 degrees Celsius) to normothermia or the standard of care (36 - 38 degrees Celsius). Data were collected using the Covidence systematic review software. Statistical analysis was performed by Review Manager software. Risk of bias, sensitivity, and heterogeneity were analyzed using the Cochran's Collaboration tool, trial sequential analysis (TSA) software, and I2 statistic respectively. Results: A total of 1825 studies were screened and 5 studies (n=3614) were included. No significant differences existed between the hypothermia group and normothermia for favorable neurologic outcome (risk ratio [RR] 1.17, 95% confidence interval [CI] 0.97 to 1.41) or all-cause mortality (RR 0.97, 95% CI 0.89 to 1.05). When compared to normothermia, the hypothermia group had greater risk of adverse effects (RR 1.16, 95% CI 1.04 to 1.28), which was driven by the onset of arrhythmias. Subgroup analyses revealed that therapeutic hypothermia provided greater neurologic benefit in trials with a higher percentage of subjects with shockable rhythms (RR 0.73, 95% CI 0.6 to 0.88). Trial sequential analysis revealed statistical futility for therapeutic hypothermia and favorable neurologic outcome, mortality, and adverse effects. Conclusions: Therapeutic hypothermia does not provide consistent benefit in neurologic outcome or mortality in the general cardiac arrest population. Patients with shockable rhythms may show favorable neurologic outcome with therapeutic hypothermia and further investigation in this population is warranted. Any potential benefit associated with therapeutic hypothermia must be weighed against the increased risk of adverse effects, particularly the onset of arrhythmias.

Safety Profile of High-Dose Intravenous Push Lacosamide.

Lacosamide (LCM) is an antiseizure medication used to manage status epilepticus (SE). Previous retrospective analyses have demonstrated safety and efficiency in intravenous push (IVP) administration at 80 mg per minute. Quick administration can be achieved in a high-acuity setting without the additional time required for compounding. However, previous literature only partially represents high doses of IVP LCM, which limits the understanding of the safety profile of these doses. Our study was a single-center, retrospective, single-arm analysis of patients who received IVP LCM 300 mg or 400 mg during admission. The primary outcome was the incidence of infusion site reactions, hypotension, and bradycardia within 2 hours of IVP administration. Secondary outcomes included the incidence of PR prolongation. A total of 113 patients were evaluated for infusion site reactions. Of these, 108 patients had vital signs assessed within 2 hours of IVP LCM and could be evaluated for hypotension and bradycardia. The sample primarily consisted of LCM 400 mg IVP (85.8%). The primary outcome consisted of 7 (6.2%) infusion reactions, 12 (11.1%) hypotensive events, and no reports of bradycardia. Each adverse event was assessed using the Naranjo Adverse Drug Probability Scale. All events scored less than two, suggesting the possibility was likely related to factors other than the medication. In conclusion, LCM 300 mg and 400 mg IVP administration have the potential to facilitate more rapid treatment of seizures without additional risk of infusion site reactions, hypotension, and bradycardia.

Burn Injury and Augmented Renal Clearance: A Case for Optimized Piperacillin-Tazobactam Dosing.

Patients with burn injuries are at high risk for infection as well as altered antimicrobial pharmacokinetics. Patients suffering from a burn injury, generally encompassing a total body surface area (TBSA) ≥ 20%, have been cited as at risk for augmented renal clearance (ARC). Our case report describes an obese patient with 3.2% TBSA partial thickness burns who suffered from burn wound cellulitis with Pseudomonas aeruginosa. Measured CLcr documented the presence of ARC, and 22.5 grams daily continuous infusion of piperacillin-tazobactam was initiated. Therapeutic monitoring of piperacillin at steady state was 78 mcg/mL, achieving the prespecified goal piperacillin concentration of 100% 4-times the minimum inhibitory concentration assuming MIC for susceptible P. aeruginosa at 16/4 mcg/mL per Clinical Laboratory Standards Institute. Available literature suggests younger critically ill patients with lower organ failure scores, and for a burn injury, a higher percentage of TBSA, are most likely to exhibit ARC which does not entirely align with the characteristics of our patient. In addition, piperacillin-tazobactam has been associated with altered pharmacokinetics in ARC, burn, and obese populations, demonstrating failure to meet target attainment with standard doses. We suggest a continuous infusion of piperacillin-tazobactam be used when ARC is identified. This case report describes the unique findings of ARC in a non-critically ill burn patient and rationalizes the need for further prospective research to classify incidence, risk factors, and appropriate antimicrobial regimens for burn patients with ARC.

Factor-guided diagnosis of coagulopathy associated with coumarin-contaminated synthetic cannabinoids.

Contamination of synthetic cannabinoids with toxic coumarin derivatives known as superwarfarins can induce a persistent coagulopathy. In comparison to warfarin, these derivatives have prolonged half-lives and laboratory assays for detection are not readily available in clinical practice. To our knowledge, factor-guided diagnosis of coagulopathy secondary to coumarin-contaminated synthetic cannabinoids has not been described previously. Our case report details a young adult who presented to the hospital with an acute elevation in INR without any reported past medical history or illicit substance use. Factor levels were obtained and resulted quickly revealing deficiencies in factors II, VII, IX, and X, which led to a possible diagnosis of coagulopathy secondary to coumarin-contaminated synthetic cannabinoids. Upon further questioning, the patient admitted to use of synthetic cannabinoids. A bromadiolone assay was sent for testing, which resulted positive after patient discharge. Toxic coumarin derivative assays are not immediately available for reference. Given the patient's confirmed synthetic cannabinoid consumption and the possibility of coagulopathy from coumarin-contamination, factor levels served as a guide for diagnosis and treatment prior to the confirmatory assay. Obtaining factor levels in patients with an unexplained coagulopathy and suspected cannabis or synthetic cannabinoid use may aid clinicians in a more prompt diagnosis and treatment.