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3.
J Med Toxicol ; 16(3): 284-294, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32356252

RESUMO

SARS-CoV-2 is a novel coronavirus that emerged in 2019 and is causing the COVID-19 pandemic. There is no current standard of care. Clinicians need to be mindful of the toxicity of a wide variety of possibly unfamiliar substances being tested or repurposed to treat COVID-19. The United States Food and Drug Administration (FDA) has provided emergency authorization for the use of chloroquine and hydroxychloroquine. These two medications may precipitate ventricular dysrhythmias, necessitating cardiac and electrolyte monitoring, and in severe cases, treatment with epinephrine and high-doses of diazepam. Recombinant protein therapeutics may cause serum sickness or immune complex deposition. Nucleic acid vaccines may introduce mutations into the human genome. ACE inhibitors and ibuprofen have been suggested to exacerbate the pathogenesis of COVID-19. Here, we review the use, mechanism of action, and toxicity of proposed COVID-19 therapeutics.

6.
Am J Emerg Med ; 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32448773

RESUMO

BACKGROUND: Patients who present with atrial fibrillation (AF) or flutter with rapid ventricular response (RVR) and hemodynamic stability may be managed with either an intravenous (IV) nondihydropyridine calcium channel blocker (CCB) or a beta-blocker (BB). Patients without improved heart rates may need to switch to, or add, a second AV nodal blocker. OBJECTIVE: To evaluate the incidence of rate control achievement and bradycardia in patients in AF or atrial flutter with RVR who receive both an intravenous CCB and a BB. METHODS: A retrospective chart review of patients who received concomitant intravenous CCB or BB for the treatment of rapid AF or atrial flutter from April 2016 through July 2018 in the emergency department. Patients were excluded if the second agent was ordered but not administered, or if they received IV amiodarone or digoxin. RESULTS: A total of 136 patients were included in the analysis, and of those, 46% (n = 62) of patients achieved a heart rate <110 bpm without bradycardia, and 3.7% (n = 5) developed bradycardia. Age, initial heart rate, time between CCB and BB administration, addition of an oral CCB or BB administration, or administration of IV magnesium did not impact target heart rate achievement. CONCLUSION: Adding a second nodal blocker in patients who did not achieve rate control with the first agent resulted in heart rate control 46% of the time. The development of symptomatic bradycardia was uncommon.

9.
J Thromb Haemost ; 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32291874

RESUMO

BACKGROUND/OBJECTIVE: Before approval of andexanet alfa, off-label treatment with 4-factor prothrombin complex concentrate (4F-PCC) was often utilized for the management of life-threatening hemorrhages associated with oral factor Xa inhibitors. We evaluated the operational processes and outcomes of patients with oral factor Xa inhibitor-associated intracranial hemorrhages (ICH) treated with andexanet alfa or 4F-PCC. METHODS: We performed a retrospective, single-center case series of rivaroxaban or apixaban-associated ICH between 2016-2019 treated with andexanet alfa or 4F-PCC. Good or excellent hemostatic effectiveness, good functional outcome (Glasgow Outcome Score [GOS]> 3) at hospital discharge, and incidence of thrombosis within 30 days were reported. RESULTS: Eighteen patients were included in the andexanet alfa cohort and 11 in the 4F-PCC cohort. Excellent or good hemostasis occurred in 88.9% of andexanet alfa-treated patients and 60% of 4F-PCC-treated patients. Good functional outcome on discharge occurred in 55.6% of andexanet alfa-treated patients and 9.1% of 4F-PCC-treated patients. Thrombotic complications occurred in 16.7% of andexanet alfa-treated patients and 9.1% of 4F-PCC-treated patients. Median order-to-administration time was 1.1 hours [0.8-1.4] versus 0.5 hours [0.1-0.8] in the andexanet alfa and 4F-PCC group, respectively. The median cost of therapy was $29970/patient versus $6925/patient in the andexanet alfa and 4F-PCC group, respectively. CONCLUSIONS: We observed higher rates of occurrence of good or excellent hemostasis and GOS > 3 on hospital discharge and increased incidence of thrombosis in patients who received andexanet alfa compared to 4F-PCC for oral factor Xa inhibitor reversal. However, patients receiving 4F-PCC had lower pre-reversal Glasgow Coma Scale (GCS)score and larger pre-reversal ICH volume.

10.
J Emerg Med ; 58(2): 203-210, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32178960

RESUMO

BACKGROUND: Poor adherence to evidence-based guidelines and overuse of broad-spectrum antibiotics has been noted in the emergency department (ED). There is limited evidence on guideline-congruent empiric therapy for urinary tract infections (UTIs) and uropathogen susceptibilities in the ED observation unit (EDOU). OBJECTIVE: The primary objective was to evaluate the prescribing patterns for the empiric treatment of UTI in the EDOU. Secondary objectives were to analyze uropathogen susceptibilities in the EDOU and implement an algorithm for the empiric treatment of UTI. METHODS: This study retrospectively reviewed adult patients who received empiric UTI treatment in the EDOU from January 1, 2018 to April 1, 2018. Eligible patients were categorized as having either uncomplicated or complicated cystitis, or pyelonephritis based on their clinical diagnosis. Antimicrobial therapy was evaluated in accordance with national practice guidelines, institutional guidelines, and local antimicrobial susceptibility patterns. RESULTS: Patients with uncomplicated or complicated cystitis (n = 115) were provided guideline-congruent empiric treatment in 87% of cases. Patients with pyelonephritis (n = 35) were provided guideline-congruent empiric treatment in 57% of cases. Susceptibility patterns of uropathogens isolated from this patient sample differed slightly from the institutional antibiogram, notably depicting a lower Escherichia coli susceptibility rate. Fluoroquinolones were prescribed for a longer than recommended duration in 18 patients (60%). CONCLUSIONS: The majority of patients in this study were provided guideline-congruent empiric therapy. Nevertheless, there are opportunities to optimize empiric UTI treatment and improve antibiotic stewardship in the EDOU.

12.
Expert Rev Hematol ; 13(2): 155-173, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31958251

RESUMO

Introduction: The emergence of the direct oral anticoagulants (DOACs) offers patients more convenient and accessible alternatives to warfarin or parenteral agents for the treatment of venous thromboembolism (VTE). Apixaban (Eliquis®) is an oral, direct factor Xa inhibitor that is approved for the acute treatment of deep-vein thrombosis (DVT) and pulmonary embolism (PE) as well as for the reduction in the risk of recurrent DVT and PE following initial therapy.Areas covered: This article reviews results from preclinical and healthy volunteer studies, large phase III trials evaluating the safety and efficacy of apixaban, as well as key studies that led to apixaban's current licensing. This review also will provide an overview of special populations where future areas of research are needed.Expert commentary: Apixaban offers several advantages over historical therapy for the treatment and secondary prevention of VTE. However, there are some populations in which the use of apixaban has not been extensively studied such as patients >75 years old, or those with cancer, low or high body weight, or poor renal function. Likewise, there is a dearth of data on pediatric patients and patients with a history of heparin-induced thrombocytopenia or identified forms of thrombophilia. Additional comparator studies on anticoagulation reversal involving andexanet alfa are also necessary to further assess its hemostatic efficacy and prothrombotic risk.

13.
Clin Toxicol (Phila) ; 58(4): 294-298, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31335216

RESUMO

Introduction: Rapid sedation of severely agitated patients is often necessary to ensure the safety of patients and healthcare workers. Intramuscular (IM) ketamine 4-6 mg/kg was previously studied but may carry an increased risk of intubation and other adverse effects. Therefore, the purpose of this case series was to describe the efficacy and safety of a reduced-dose (2 mg/kg) IM ketamine guideline.Methods: Consecutive patients receiving IM ketamine for agitation in the emergency department via our reduced-dose guideline were included. Successful sedation of the agitated patient was defined as documentation from a healthcare provider, a lack of additional sedating medication administration for 30 min following administration of IM ketamine, or ability to complete necessary procedure.Results: Of 15 patients included in this case series, 13 (87%) were adequately sedated with no subsequent intubations due to excess ketamine. The median total dose administered was 157.5 mg and the median weight-based dose was 2 mg/kg. In 11 of the 15 cases, reduced-dose ketamine was used as a second-line agent.Conclusion: Reduced-dose IM ketamine may be effective for severe agitation, particularly when used as a second-line agent.

14.
Toxicol Commun ; 3(1): 79-84, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31745533

RESUMO

Methylene chloride is a volatile, chlorinated hydrocarbon and colorless solvent found in multiple industrial products including paint strippers, metal cleaners, automotive products, pesticides and aerosol containers. Occupational exposure to methylene chloride is reported in automotive technicians, painters, and other industrial workers with adverse health effects including gastrointestinal, neurological, as well as hepato-renal injuries. International Agency for Research on Cancer (IARC) classifies methylene chloride as a 2 A carcinogen. Through a series of reactions catalyzed by cytochrome P450 2E1 (CYP2E1), metabolism of methylene chloride leads to the formation of formyl chloride, and ultimately carbon monoxide (CO). Most reports of methylene chloride toxicity are due to dermal and inhalational exposure in occupational settings. Ingestion of methylene chloride is uncommon, yet can lead to significant toxicity and prolonged CO toxicity. Methylene chloride is frequently formulated with methanol; individuals who intentionally ingest methylene chloride can experience concomitant methanol toxicity. We present a case of acute ingestion of paint stripper containing methanol and methylene chloride. We discuss the clinical presentation, key management decisions, relevant pathophysiology and biochemistry, as well as the clinical course and management.

15.
West J Emerg Med ; 20(4): 619-625, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31316701

RESUMO

Introduction: Warfarin is a potent anticoagulant used for the prevention and treatment of venous and arterial thrombosis. Occasionally, patients require emergent warfarin reversal due to active bleeding, supratherapeutic international normalized ratio, or emergent diagnostic or therapeutic interventions. Various agents can be used for emergent warfarin reversal, including fresh frozen plasma (FFP) and 4-factor prothrombin complex concentrate (4F-PCC). Both FFP and 4F-PCC are generally considered safe; however, both agents contain coagulation factors and have the potential to provoke a thromboembolic event. Although clinical trials have compared the efficacy and safety of FFP and 4F-PCC, data are limited comparing the risk of thromboembolism between the two agents. Methods: A retrospective chart review was performed at a single, urban, academic medical center comparing the incidence of thromboembolism with FFP or 4F-PCC for warfarin reversal during a three-year period in the emergency department (ED) at Massachusetts General Hospital. Patients were included in the study if they were at least 18 years of age and were on warfarin per electronic health records. Patients were excluded if they had received both FFP and 4F-PCC during the same visit. The primary outcome was the frequency of thromboembolism within 30 days of 4F-PCC or FFP. Secondary outcomes included time to thromboembolic event and in-hospital mortality. Results: Three hundred and thirty-six patients met the inclusion criteria. Thromboembolic events within 30 days of therapy occurred in seven patients (2.7%) in the FFP group and 14 patients (17.7%) in the 4F-PCC group (p=<0.001). Death occurred in 39 patients (15.2%) who received FFP and 18 patients (22.8%) who received 4F-PCC (p=0.115). Since the 4F-PCC group was treated disproportionately for central nervous system (CNS) bleeding, a subgroup analysis was performed including patients requiring reversal due to CNS bleeds that received vitamin K. The primary outcome remained statistically significant, occurring in four patients (4.1%) in the FFP group and nine patients (14.1%) in the 4F-PCC group (p=0.02). Conclusion: Our study found a significantly higher risk of thromboembolic events in patients receiving 4F-PCC compared to FFP for urgent warfarin reversal. This difference remained statistically significant when controlled for CNS bleeds and administration of vitamin K.


Assuntos
Fatores de Coagulação Sanguínea/efeitos adversos , Plasma , Tromboembolia/induzido quimicamente , Idoso , Anticoagulantes/efeitos adversos , Fatores de Coagulação Sanguínea/administração & dosagem , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Estudos Retrospectivos , Tromboembolia/epidemiologia , Varfarina/efeitos adversos
18.
Hosp Pharm ; 53(5): 326-330, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30210151

RESUMO

Purpose: The aim of this study was to compare Plasma-Lyte A (PL) and sodium chloride 0.9% (NS) in regard to time to resolution of diabetic ketoacidosis (DKA) when one fluid was used predominantly over the other for resuscitation. Methods: We performed a retrospective analysis of the records of patients treated for DKA at a large, academic medical center between July 1, 2013, and July 1, 2015. Patients were placed into the PL or NS group based on the predominant fluid they received during fluid resuscitation. Serum biochemistry variables were categorized as follows: initial, 2 to 4 hours, 4 to 6 hours, 6 to 12 hours, and 12 to 24 hours. The primary outcome was mean time to resolution of DKA. Results: Eighty-four patients were included in the study. The primary outcome of mean time to resolution of DKA was similar between the PL (19.74 hours) and NS (18.05 hours) groups (P = .5080). Patients treated with PL had a significantly greater rise in pH within the 4- to 6-hour and 6- to 12-hour periods. The chloride level was significantly higher and the anion gap was significantly lower for the NS group in the 6- to 12-hour period. Conclusion: These data suggest that the use of PL for fluid resuscitation in DKA may confer certain advantages over NS.

19.
West J Emerg Med ; 19(5): 849-854, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30202498

RESUMO

Introduction: Advancements in the treatment of warfarin-associated intracranial hemorrhage (ICH) include the use of four-factor prothrombin complex concentrate (4F-PCC), which has demonstrated more rapid reversal of the international normalized ratio (INR) when compared with fresh frozen plasma. A pharmacist-driven protocol for 4F-PCC was implemented within our institution, which allows for pharmacist approval of 4F-PCC in patients diagnosed with warfarin-associated ICH and an INR ≥2. The pharmacist is responsible for determining the appropriate dose of 4F-PCC, preparation, bedside delivery, and order entry into the electronic medical record. Prior to implementation of the new protocol, the blood bank was responsible for 4F-PCC approval, dosing, product preparation, and arranging delivery with emergency department (ED) staff. The purpose of this study was to evaluate the impact of a pharmacist-driven protocol on time to 4F-PCC administration in warfarin-associated ICH. Methods: We performed a retrospective review of consecutive patients who received 4F-PCC in a single ED from September 2015 through February 2017. Patients ≥18 years old were eligible for inclusion based on three criteria: confirmed diagnosis of ICH; confirmed warfarin use; and INR ≥2. Secondary outcomes included dose of 4F-PCC in concordance with INR and weight-based dosing recommendations and hospital protocol, as well as concomitant intravenous vitamin K administration. Results: A total of 48 patients met inclusion criteria for the study with 24 patients in each protocol group. The median time to administration of 4F-PCC in the pharmacist-driven protocol group was 35 minutes (interquartile range [IQR] [25-62]; range, 11-133) compared with 70 minutes (IQR [34-89]; range, 14-244) in the pre-protocol group (p=0.034). We saw no differences for appropriate 4F-PCC dosing based on INR and patient weight between the two groups. Conclusion: Implementation of a pharmacist-driven protocol for 4F-PCC in the ED at our institution significantly reduced time to administration in patients presenting with warfarin-associated ICH.


Assuntos
Anticoagulantes/efeitos adversos , Fatores de Coagulação Sanguínea/uso terapêutico , Hemorragias Intracranianas/tratamento farmacológico , Farmacêuticos , Varfarina/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Coeficiente Internacional Normatizado , Hemorragias Intracranianas/induzido quimicamente , Masculino , Estudos Retrospectivos , Fatores de Tempo
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