RESUMO
BACKGROUND: Cefepime is a widely used antibiotic with neurotoxicity attributed to its ability to cross the blood-brain barrier and exhibit concentration-dependent Ï-aminobutyric acid (GABA) antagonism. Neurotoxic symptoms include depressed consciousness, encephalopathy, aphasia, myoclonus, seizures, and coma. Data suggest that up to 15% of ICU patients treated with cefepime may experience these adverse effects. Risk factors include renal dysfunction, excessive dosing, preexisting brain injury, and elevated serum cefepime concentrations. We aimed to characterize the clinical course of cefepime neurotoxicity and response to interventions. METHODS: A librarian-assisted search identified publications describing cefepime-associated neurotoxicity from January 1980 to February 2016 using the CINAHL and MEDLINE databases. Search terms included cefepime, neurotoxicity, encephalopathy, seizures, delirium, coma, non-convulsive status epilepticus, myoclonus, confusion, aphasia, agitation, and death. Two reviewers independently assessed identified articles for eligibility and used the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) for data reporting. RESULTS: Of the 123 citations identified, 37 (representing 135 patient cases) were included. Patients had a median age of 69 years, commonly had renal dysfunction (80%) and required intensive care (81% of patients with a reported location). All patients exhibited altered mental status, with reduced consciousness (47%), myoclonus (42%), and confusion (42%) being the most common symptoms. All 98 patients (73% of cohort) with electroencephalography had abnormalities, including non-convulsive status epilepticus (25%), myoclonic status epilepticus (7%), triphasic waves (40%), and focal sharp waves (39%). As per Food and Drug Administration (FDA)-approved dosing guidance, 48% of patients were overdosed; however, 26% experienced neurotoxicity despite appropriate dosing. Median cefepime serum and cerebrospinal fluid (CSF) concentrations were 45 mg/L (n = 21) and 13 mg/L (n = 4), respectively. Symptom improvement occurred in 89% of patients, and 87% survived to hospital discharge. The median delay from starting the drug to symptom onset was 4 days, and resolution occurred a median of 2 days after the intervention, which included cefepime discontinuation, antiepileptic administration, or hemodialysis. CONCLUSIONS: Cefepime-induced neurotoxicity is challenging to recognize in the critically ill due to widely varying symptoms that are common in ICU patients. This adverse reaction can occur despite appropriate dosing, usually resolves with drug interruption, but may require additional interventions such as antiepileptic drug administration or dialysis.
Assuntos
Cefalosporinas/efeitos adversos , Síndromes Neurotóxicas/etiologia , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Cefepima , Cefalosporinas/uso terapêutico , Transtornos da Consciência/induzido quimicamente , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Humanos , Síndromes Neurotóxicas/complicações , Síndromes Neurotóxicas/fisiopatologia , Convulsões/induzido quimicamenteAssuntos
Anticoagulantes/efeitos adversos , Fatores de Coagulação Sanguínea/efeitos adversos , Hemorragia Gastrointestinal/tratamento farmacológico , Hemostáticos/efeitos adversos , Acidente Vascular Cerebral/induzido quimicamente , Trombose/induzido quimicamente , Varfarina/efeitos adversos , Idoso de 80 Anos ou mais , Fatores de Coagulação Sanguínea/uso terapêutico , Trombose Coronária/induzido quimicamente , Trombose Coronária/diagnóstico , Feminino , Veia Femoral , Hemorragia Gastrointestinal/induzido quimicamente , Hemostáticos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/diagnóstico , Trombose/diagnóstico , Trombose Venosa/induzido quimicamente , Trombose Venosa/diagnósticoRESUMO
BACKGROUND AND PURPOSE: Despite a paucity of evidence supporting a true association of ischemic stroke and the inherited thrombophilias, it is common practice for many neurologists to order these tests as part of the work-up of ischemic stroke, especially in young patients. Treatment with oral anticoagulation is often used in patients with positive results for the inherited thrombophilias. METHODS: We reviewed the literature focusing on case-control studies of the 5 most commonly inherited disorders of coagulation: protein C deficiency, protein S deficiency, antithrombin deficiency, and the factor V Leiden and prothrombin gene mutations in patients with stroke. We also analyzed the available data on stroke patients with inherited thrombophilia and patent foramen ovale. RESULTS: Multiple case-control studies have not convincingly shown an association of the inherited thrombophilias with ischemic stroke, even in young patients and patients with patent foramen ovale. CONCLUSIONS: If there is an association between the inherited thrombophilias and arterial stroke, then it is a weak one, likely enhanced by other prothrombotic risk factors. The consequences of ordering these tests and attributing causality to an arterial event can result in significant costs to the health care system and pose a potential risk to patients, because this may lead to inappropriate use of long-term oral anticoagulants, exposing patients to harm without a clearly defined benefit.
Assuntos
Acidente Vascular Cerebral/diagnóstico , Trombofilia/diagnóstico , Deficiência de Antitrombina III/genética , Deficiência de Antitrombina III/patologia , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/genética , Estudos de Casos e Controles , Análise Custo-Benefício , Deficiência do Fator V/genética , Deficiência do Fator V/patologia , Forame Oval Patente/complicações , Forame Oval Patente/patologia , Humanos , Deficiência de Proteína C/genética , Deficiência de Proteína C/patologia , Deficiência de Proteína S/genética , Deficiência de Proteína S/patologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/genética , Trombofilia/complicações , Trombofilia/genéticaRESUMO
BACKGROUND AND PURPOSE: Discovering potential cardiac sources of stroke is an important part of the urgent evaluation of the ischemic stroke patient as it often impacts treatment decisions that are essential for determining secondary stroke prevention strategies, yet the optimal approach to the cardiac workup of an ischemic stroke patient is not known. METHODS: A review of the literature concerning the utility of cardiac rhythm monitoring (ECG, telemetry, Holter monitors, and event recorders) and structural imaging (transthoracic and transesophageal echocardiography) was performed. RESULTS: Data supporting a definitive, optimal, and cost-effective approach are lacking, though some data suggest that appropriate patient selection can improve the diagnostic and therapeutic yield of rhythm monitoring and echocardiography in the evaluation of stroke etiology. CONCLUSIONS: Based on available data, an algorithmic approach for the evaluation of patients with acute ischemic cerebrovascular events that takes into account therapeutic and diagnostic yield as well as cost-efficiency is proposed.
Assuntos
Isquemia Encefálica/diagnóstico , Isquemia Encefálica/fisiopatologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Adulto , Depressão Alastrante da Atividade Elétrica Cortical/fisiologia , Eletrocardiografia/métodos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Time is of the essence when a patient has signs and symptoms suggestive of a stroke or TIA. What should your initial approach and diagnostic work-up be?
Assuntos
Continuidade da Assistência ao Paciente/organização & administração , Medicina Geral/métodos , Clínicos Gerais , Ataque Isquêmico Transitório/terapia , Acidente Vascular Cerebral/terapia , Humanos , Índice de Gravidade de DoençaRESUMO
A multifactorial approach is key to effective secondary stroke prevention. Here's how to individualize your plan for your at-risk patients.
Assuntos
Aspirina/uso terapêutico , Medicina de Família e Comunidade/métodos , Ataque Isquêmico Transitório/prevenção & controle , Inibidores da Agregação Plaquetária/uso terapêutico , Prevenção Secundária/métodos , Acidente Vascular Cerebral/prevenção & controle , HumanosAssuntos
Neoplasias do Sistema Nervoso Central/complicações , Fibrinolíticos/uso terapêutico , Hemangioma Cavernoso do Sistema Nervoso Central/complicações , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico , Idoso , Humanos , Masculino , Acidente Vascular Cerebral/complicações , Terapia TrombolíticaRESUMO
Isolated cortical subarachnoid hemorrhage is rare and poorly understood. Differential diagnoses and proposed pathophysiology vary widely and the diagnostic work-up for these patients who present with transient ischemic attack-like episodes and characteristic imaging findings is still unclear. We report a case of isolated subarachnoid hemorrhage and transient neurologic deficits due to isolated cortical vein thrombosis that was not detected by noninvasive tests. A 75-year-old woman with a history of a lobar intracerebral hemorrhage presented to the Academic Medical Center with sudden-onset transient left upper extremity weakness. Head CT showed a linear hyperdensity in the right precentral gyrus suggestive of isolated subarachnoid hemorrhage. MRI showed susceptibility in the corresponding area. CT angiogram and MRV showed no evidence of a venous thrombosis. The main outcome measures were results of computerized tomography and CT angiogram, magnetic resonance parenchymal and vascular imaging, angiography findings and clinical follow-up at 3 months. Cortical vein thrombosis was detected on conventional angiography. MRI was negative for microhemorrhages. The patient was anticoagulated and had no recurrences of her symptoms. We conclude that cortical vein thrombosis can present as isolated subarachnoid hemorrhage and transient ischemic attack-like episodes and may require angiography for definitive diagnosis.