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Introduction: Evidence for optimal analgesia following subarachnoid hemorrhage (SAH) is limited. Steroid therapy for pain refractory to standard regimens is common despite lack of evidence for its efficacy. We sought to determine if steroids reduced pain or utilization of other analgesics when given for refractory headache following SAH. Methods: We performed a retrospective within-subjects cohort study of SAH patients who received steroids for refractory headache. We compared daily pain scores, total daily opioid, and acetaminophen doses before, during, and after steroids. Repeated measures were analyzed with a multivariable general linear model and generalized estimating equations. Results: Included 52 patients treated with dexamethasone following SAH, of whom 11 received a second course, increasing total to 63 treatment epochs. Mean pain score on the first day of therapy was 7.92 (standard error of the mean [SEM] .37) and decreased to 6.68 (SEM .36) on the second day before quickly returning to baseline levels, 7.36 (SEM .33), following completion of treatment. Total daily analgesics mirrored this trend. Mean total opioid and acetaminophen doses on days one and two and two days after treatment were 47.83mg (SEM 6.22) and 1848mg (SEM 170.66), 34.24mg (SEM 5.12) and 1809mg (SEM 150.28), and 46.38mg (SEM 11.64) and 1833mg (SEM 174.23), respectively. Response to therapy was associated with older age, decreasing acetaminophen dosing, and longer duration of steroids. Hyperglycemia and sleep disturbance/delirium effected 28.6% and 55.6% of cases, respectively. Conclusion: Steroid therapy for refractory pain in SAH patients may have modest, transient effects in select patients.
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ABSTRACT: In this study, we hypothesized that immersive virtual reality (VR) environments may reduce pain in patients with acute traumatic injuries, including traumatic brain injuries. We performed a randomized within-subject study in patients hospitalized with acute traumatic injuries, including traumatic brain injury with moderate pain (numeric pain score ≥3 of 10). We compared 3 conditions: (1) an immersive VR environment (VR Blu), (2) a content control with the identical environment delivered through nonimmersive tablet computer (Tablet Blu), and (3) a second control composed of donning VR headgear without content to control for placebo effects and sensory deprivation (VR Blank). We enrolled 60 patients, and 48 patients completed all 3 conditions. Objective and subjective data were analyzed using linear mixed-effects models. Controlling for demographics, baseline pain, and injury severity, we found differences by conditions in relieving pain (F 2,75.43 = 3.32, P = 0.042). VR Blu pain reduction was greater than Tablet Blu (-0.92 vs -0.16, P = 0.043), but VR Blu pain reduction was similar to VR Blank (-0.92 vs -1.24, P = 0.241). VR Blu was perceived as most effective by patients for pain reduction (F 2,66.84 = 16.28, P < 0.001), and changes in measures of parasympathetic activity including heart rate variability (F 2,55.511 = 7.87, P < 0.001) and pupillary maximum constriction velocity (F 2,61.41 = 3.50, 1-tailed P = 0.038) echoed these effects. There were no effects on opioid usage. These findings outlined a potential clinical benefit for mollifying pain related to traumatic injuries.
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Lesões Encefálicas Traumáticas , Realidade Virtual , Humanos , Manejo da Dor , Medição da Dor , Dor/etiologia , Lesões Encefálicas Traumáticas/complicaçõesRESUMO
BACKGROUND: Nimodipine improves outcomes following aneurysmal subarachnoid hemorrhage (aSAH) and current guidelines suggest that patients with aSAH receive nimodipine for 21 days. Patients with no difficulty swallowing will swallow the whole capsules or tablets; otherwise, nimodipine liquid must be drawn from capsules, tablets need to be crushed, or the commercially available liquid product be used to facilitate administration through an enteral feeding tube (FT). It is not clear whether these techniques are equivalent. The goal of the study was to determine if different nimodipine formulations and administration techniques were associated with the safety and effectiveness of nimodipine in aSAH. METHODS: This was a retrospective multicenter observational cohort study conducted in 21 hospitals across North America. Patients admitted with aSAH and received nimodipine by FT for ≥3 days were included. Patient demographics, disease severity, nimodipine administration, and study outcomes were collected. Safety end points included the prevalence of diarrhea and nimodipine dose reduction or discontinuation secondary to blood pressure reduction. Predictors of the study outcomes were analyzed using regression modeling. RESULTS: A total of 727 patients were included. Administration of nimodipine liquid product was independently associated with higher prevalence of diarrhea compared to other administration techniques/formulations (Odds ratio [OR] 2.28, 95% confidence interval [CI] 1.41-3.67, p-value = 0.001, OR 2.76, 95% CI 1.37-5.55, p-value = 0.005, for old and new commercially available formulations, respectively). Bedside withdrawal of liquid from nimodipine capsules prior to administration was significantly associated with higher prevalence of nimodipine dose reduction or discontinuation secondary to hypotension (OR 2.82, 95% CI 1.57-5.06, p-value = 0.001). Tablet crushing and bedside withdrawal of liquid from capsules prior to administration were associated with increased odds of delayed cerebral ischemia (OR 6.66, 95% CI 3.48-12.74, p-value <0.0001 and OR 3.92, 95% CI 2.05-7.52, p-value <0.0001, respectively). CONCLUSIONS: Our findings suggest that enteral nimodipine formulations and administration techniques might not be equivalent. This could be attributed to excipient differences, inconsistency and inaccuracy in medication administration, and altered nimodipine bioavailability. Further studies are needed.
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Hipotensão , Hemorragia Subaracnóidea , Humanos , Nimodipina/efeitos adversos , Hemorragia Subaracnóidea/tratamento farmacológico , Bloqueadores dos Canais de Cálcio/efeitos adversos , Estudos Retrospectivos , Nutrição Enteral/efeitos adversos , Comprimidos/uso terapêuticoRESUMO
PURPOSE: The purpose of this study was to gauge postgraduate year 1 (PGY1) pharmacy residency candidates' reactions to supplemental applications, as well as aspects specific to our process, including a personality test and situational judgment test (SJT). METHODS: After rank lists were submitted, applicants to our program were invited to complete an online survey. Outcomes of interest included candidates' perceptions of relevance and fairness. Whether candidates' attitudes differed based on the receipt of an interview offer was also assessed. RESULTS: Of 199 applicants to our program for the 2021-2022 training year, 48 applicants (24.1%) completed the survey, 15 of whom had received an interview offer. Most (64.6%) agreed that supplemental applications were useful, and nearly all (95.8%) indicated that they were willing to submit one for programs in which they were most interested. The process was seen as being fair, although ratings were higher among those who received interview offers. Most respondents believed that the personality test and SJT were relevant to the role of a resident, but attitudes towards the SJT were generally more favorable and less likely to vary according to whether candidates received an interview offer. Candidates believed that the personality test and SJT were not as representative of them as letters of reference or their curriculum vitae, but perceptions of academic performance varied. CONCLUSION: Applicants responded positively to our supplemental application and indicated that they would be willing to complete one for programs of interest. These findings should help assuage concerns about the use of supplemental applications, particularly when short-answer or essay formats are avoided.
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Internato e Residência , Residências em Farmácia , Humanos , Julgamento , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Prompt diagnosis and intervention for ventilator-associated pneumonia (VAP) is critical but can lead to overdiagnosis and overtreatment. OBJECTIVES: We investigated healthcare provider (HCP) perceptions and challenges associated with VAP diagnosis, and we sought to identify opportunities for diagnostic stewardship. METHODS: We conducted a qualitative study of 30 HCPs at a tertiary-care hospital. Participants included attending physicians, residents and fellows (trainees), advanced practice providers (APPs), and pharmacists. Interviews were composed of open-ended questions in 4 sections: (1) clinical suspicion and thresholds for respiratory culture ordering, (2) preferences for respiratory sample collection, (3) culture report interpretation, and (4) VAP diagnosis and treatment. Interviews transcripts were analyzed using Nvivo 12 software, and responses were organized into themes. RESULTS: Overall, 10 attending physicians (75%) and 16 trainees (75%) trainees and APPs believed they were overdiagnosing VAP; this response was frequent among HCPs in practice 5-10 years (91%, n = 12). Increased identification of bacteria as a result of frequent respiratory culturing, misinterpretation of culture data, and fear of missing diagnosis were recognized as drivers of overdiagnosis and overtreatment. Although most HCPs rely on clinical and radiographic changes to initiate work-up, the fear of missing a diagnosis leads to sending cultures even in the absence of those changes. CONCLUSIONS: HCPs believe that VAP overdiagnosis and overtreatment are common due to fear of missing diagnosis, overculturing, and difficulty distinguishing colonization from infection. Although we identified opportunities for diagnostic stewardship, interventions influencing the ordering of cultures and starting antimicrobials will need to account for strongly held beliefs and ICU practices.
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Pneumonia Associada à Ventilação Mecânica , Cuidados Críticos , Pessoal de Saúde , Humanos , Unidades de Terapia Intensiva , Farmacêuticos , Pneumonia Associada à Ventilação Mecânica/diagnóstico , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Pneumonia Associada à Ventilação Mecânica/microbiologia , Sistema RespiratórioRESUMO
PURPOSE: This study assessed whether personality testing of postgraduate year 1 (PGY1) pharmacy residency applicants was feasible and predicted important selection outcomes, including interview offers. METHODS: Applicants to the PGY1 pharmacy residency program at a large academic medical center were invited to complete a 50-item online personality test based on the 5-factor model (ie, the "Big Five"). Scores were sealed until after matching, at which point they were compared to screening, interview, and ranking and match outcomes. Endpoints of interest included the feasibility of the test (eg, time required for completion, completion rate) and whether personality predicted the odds of an interview offer. RESULTS: The personality test was taken by 137 PGY1 applicants (69.5%) and required a median of 6.8 minutes to complete. Openness to experience was associated with decreased odds of an interview offer (adjusted odds ratio [OR], 0.86; 95% confidence interval [CI], 0.75-0.98), whereas conscientiousness and extraversion were associated with increased odds of an interview offer (conscientiousness: adjusted OR, 1.26; 95% CI, 1.02-1.55; extraversion: OR, 1.16; 95% CI, 1.03-1.31). When combined with traditional screening criteria (eg, awards, leadership positions), openness to experience and extraversion remained predictors of an interview offer (in the directions specified above), whereas conscientiousness did not. In an exploratory analysis of interviewees, agreeableness was a negative predictor of interview score. Personality did not predict screening scores or final ranking. CONCLUSION: Personality testing, based on the traits desired at individual residency programs, could be a valuable addition to the methods used for selecting PGY1 pharmacy residents.
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Residências em Farmácia , Farmácia , Estudantes de Farmácia , Humanos , Liderança , PersonalidadeRESUMO
BACKGROUND: Subarachnoid hemorrhage (SAH) is characterized by the worst headache of life and associated with long-term opioid use. Discrete pain trajectories predict chronic opioid use following other etiologies of acute pain, but it is unknown whether they exist following SAH. If discrete pain trajectories following SAH exist, it is uncertain whether they predict long-term opioid use. We sought to characterize pain trajectories after SAH and determine whether they are associated with persistent opioid use. METHODS: We reviewed pain scores from patients admitted to a single tertiary care center for SAH from November 2015 to September 2019. Group-based trajectory modeling identified discrete pain trajectories during hospitalization. We compared outcomes across trajectory groups using χ2 and Kruskal-Wallis tests. Multivariable regression determined whether trajectory group membership was an independent predictor of long-term opioid use, defined as continued use at outpatient follow-up. RESULTS: We identified five discrete pain trajectories among 305 patients. Group 1 remained pain free. Group 2 reported low scores with intermittent spikes and slight increase over time. Group 3 noted increasing pain severity through day 7 with mild improvement until day 14. Group 4 experienced maximum pain with steady decrement over time. Group 5 reported moderate pain with subtle improvement. In multivariable analysis, trajectory groups 3 (odds ratio [OR] 3.5; 95% confidence interval [CI] 1.5-8.3) and 5 (OR 8.0; 95% CI 3.1-21.1), history of depression (OR 3.6; 95% CI 1.3-10.0) and racial/ethnic minority (OR 2.3; 95% CI 1.3-4.1) were associated with continued opioid use at follow-up (median 62 days following admission, interquartile range 48-96). CONCLUSIONS: Discrete pain trajectories following SAH exist. Recognition of pain trajectories may help identify those at risk for long-term opioid use.
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Analgésicos Opioides , Hemorragia Subaracnóidea , Analgésicos Opioides/uso terapêutico , Etnicidade , Seguimentos , Humanos , Grupos Minoritários , Pacientes Ambulatoriais , Dor/etiologia , Hemorragia Subaracnóidea/complicaçõesRESUMO
OBJECTIVE: Little is known about the prevalence of continued opioid use following aneurysmal subarachnoid hemorrhage (aSAH) despite guidelines recommending their use during the acute phase of disease. We sought to determine prevalence of opioid use following aSAH and test the hypothesis that acute pain and higher inpatient opioid dose increased outpatient opioid use. METHODS: We reviewed consecutively admitted patients with aSAH from November 2015 through September 2019. We retrospectively collected pain scores and daily doses of analgesics. Pain burden was calculated as area under the pain-time curve. Univariate and multivariable regression models determined risk factors for continued opioid use at discharge and outpatient follow-up. RESULTS: We identified 234 patients with aSAH with outpatient follow-up. Continued opioid use was common at discharge (55% of patients) and follow-up (47% of patients, median 63 [interquartile range 49-96] days from admission). Pain burden, craniotomy, and racial or ethnic minority status were associated with discharge opioid prescription in multivariable analysis. At outpatient follow-up, pain burden (odds ratio [OR] 1.88, 95% confidence interval [CI] 1.5-2.4), depression (OR 3.1, 95% CI 1.1-8.8), and racial or ethnic minority status (OR 2.1, 95% CI 1.1-4.0) were independently associated with continued opioid use; inpatient opioid dose was not. CONCLUSION: Continued opioid use following aSAH is prevalent and related to refractory pain during acute illness, but not inpatient opioid dose. More efficacious analgesic strategies are needed to reduce continued opioid use in patients following aSAH. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that continued opioid use following aSAH is associated with refractory pain during acute illness but not hospital opioid exposure.
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Dor Aguda/tratamento farmacológico , Assistência Ambulatorial/tendências , Analgésicos Opioides/administração & dosagem , Dor Intratável/tratamento farmacológico , Hemorragia Subaracnóidea/tratamento farmacológico , Dor Aguda/diagnóstico , Dor Aguda/etiologia , Adulto , Idoso , Assistência Ambulatorial/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Dor Intratável/diagnóstico , Dor Intratável/etiologia , Alta do Paciente/tendências , Estudos Prospectivos , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/diagnósticoRESUMO
OBJECTIVES: The management of patients admitted with intracerebral hemorrhage (ICH) mostly occurs in an ICU. While guidelines recommend initial treatment of these patients in a neurocritical care or stroke unit, there is limited data on which patients would benefit most from transfer to a comprehensive stroke center where on-site neurosurgical coverage is available 24/7. As neurocritical units become more common in primary stroke centers, it is important to determine which patients are most likely to require neurosurgical intervention and transfer to comprehensive stroke centers. MATERIALS AND METHODS: This is a retrospective observational cohort study conducted at an academic comprehensive stroke center in the United States. Four-hundred-fifty-nine consecutive patients transferred or directly admitted to the neurocritical care unit from 2016-2018 with the primary diagnosis of ICH were included. Univariate statistics and multivariate regression were used to identify clinical characteristics associated with neurosurgical intervention, defined as undergoing craniotomy, ventriculostomy, or endovascular embolization of an arteriovenous malformation (AVM). RESULTS: The following variables were associated with neurosurgical intervention in multivariate analysis: age (OR 0.38, 95% CI 0.27-0.55), admission Glasgow Coma Scale (OR 0.29, 95% CI 0.18-0.48), the presence of intraventricular hemorrhage (OR 2.82, CI 1.71-4.65), infratentorial location of ICH (OR 2.28, 95% CI 1.20-4.31), previous antiplatelet use (OR 2.04, 95% CI 1.24-3.34), and an AVM indicated on CT Angiogram (OR 2.59, 95% CI 1.19-5.63) were independently associated with the need for neurosurgical intervention. This was translated into a scoring system to help make quick triage decisions, with high sensitivity (99%, 95% CI 97-99%) and negative predictive value (98%, 95% CI 89-99%). CONCLUSIONS: Using previously well described predictors of severity in ICH patients, we were able to develop a scoring system to predict the need for neurosurgical intervention with high sensitivity and negative predictive value.
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Hemorragia Cerebral/cirurgia , Técnicas de Apoio para a Decisão , Prestação Integrada de Cuidados de Saúde , Procedimentos Endovasculares , Procedimentos Neurocirúrgicos , Admissão do Paciente , Transferência de Pacientes , Triagem , Idoso , Hemorragia Cerebral/diagnóstico , Tomada de Decisão Clínica , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/efeitos adversos , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
OBJECTIVE: Intravenous glyburide has demonstrated safety when used for attenuation of cerebral edema, although safety data are lacking for enteral glyburide when used for this indication. We aimed to determine the prevalence of and risk factors for hypoglycemia in neurocritical care patients receiving enteral glyburide. METHODS: We performed a retrospective case-control chart review (hypoglycemia vs. no hypoglycemia) of adult patients who received enteral glyburide for prevention or treatment of cerebral or spinal cord edema. Hypoglycemia was defined as a blood glucose <55.8 mg/dL. Descriptive statistics were used, with multivariate analysis to measure the association of risk factors and outcomes. Logistic regression was applied to outcomes with an exposure. Potential confounders were evaluated using the t-test or the Wilcoxon rank-sum test for continuous variables, and the χ2 test or the Fisher exact test for categorical variables. RESULTS: Seventy-one patients (60.6% men, median age 60 years) were included. The majority received 2.5 mg of enteral glyburide twice daily. Diagnoses included tumors (35.2%), intracerebral hemorrhage (28.2%), postspinal surgery (12.7%), and ischemic stroke (12.7%). Hypoglycemia occurred in 17 (23.9%) patients. Multivariate analysis identified admission serum creatinine (odds ratio, 27.2; [1.661, 445.3]; P < 0.05) as a risk factor for hypoglycemia, whereas body mass index >30 (odds ratio, 0.085; [0.008, 0.921]; P < 0.05) was protective. CONCLUSIONS: Hypoglycemic episodes are common following enteral glyburide in neurocritical care patients. Both patients with and without diabetes mellitus are at risk of hypoglycemia. Elevated admission serum creatinine may increase the risk of hypoglycemia when utilizing glyburide for prevention or treatment of cerebral or spinal cord edema.
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Edema Encefálico/prevenção & controle , Glibureto/uso terapêutico , Hipoglicemia/epidemiologia , Hipoglicemiantes/uso terapêutico , Doenças da Medula Espinal/prevenção & controle , Administração Oral , Adulto , Idoso , Índice de Massa Corporal , Edema Encefálico/tratamento farmacológico , Edema Encefálico/etiologia , Neoplasias do Sistema Nervoso Central/complicações , Neoplasias do Sistema Nervoso Central/terapia , Hemorragia Cerebral/complicações , Hemorragia Cerebral/terapia , Creatinina/sangue , Cuidados Críticos , Vias de Administração de Medicamentos , Edema/tratamento farmacológico , Edema/etiologia , Edema/prevenção & controle , Feminino , Humanos , Hipoglicemia/induzido quimicamente , AVC Isquêmico/complicações , AVC Isquêmico/terapia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/prevenção & controle , Fatores de Proteção , Estudos Retrospectivos , Fatores de Risco , Doenças da Medula Espinal/tratamento farmacológico , Doenças da Medula Espinal/etiologia , Coluna Vertebral/cirurgiaRESUMO
PURPOSE: Although guidelines recommend dexmedetomidine (DEX) or propofol (PRO) as preferred sedatives in critically ill adults, comparisons in neurocritical care (NCC) are limited. We aimed to evaluate the clinical utility and safety of DEX compared with PRO in NCC setting. MATERIALS AND METHODS: This retrospective, multicenter, observational cohort study conducted at three tertiary academic hospitals with Level 1 Trauma Center and Comprehensive Stroke Center designations, compared the clinical indication and safety of DEX vs PRO in patients in NCC setting. RESULTS: 179 patients were included (94 DEX and 85 PRO), median age of 58, 49% were male (DEX) and 58% were male (PRO). PRO was more commonly used to manage agitation. DEX was more commonly used for facilitating extubation, alcohol withdrawal, and sedation during frequent neurologic assessments. Mean Glasgow Coma Scale scores were higher in DEX group (11 vs. 9; p = .04). The duration of either infusions, mechanical ventilation, and lengths of stay were similar. No difference was observed in hypotension or bradycardia rates. Death was significantly higher with PRO (DEX 10% vs. PRO 22%; p = .02). CONCLUSIONS: DEX and PRO were used for distinct indications in our cohort. Adverse effect profiles and clinical outcome, in the cohorts are largely similar.
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Bradicardia/induzido quimicamente , Cuidados Críticos/métodos , Dexmedetomidina/efeitos adversos , Hipnóticos e Sedativos/efeitos adversos , Hipotensão/induzido quimicamente , Propofol/efeitos adversos , Adulto , Idoso , Estado Terminal , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Respiração Artificial , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Targeted temperature management (TTM) is used frequently in patients with a variety of diseases, especially those who have experienced brain injury and/or cardiac arrest. Shivering is one of the main adverse effects of TTM that can often limit its implementation and efficacy. Shivering is the body's natural response to hypothermia and its deleterious effects can negate the benefits of TTM. The purpose of this article is to provide an overview of TTM strategies and shivering management.
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Parada Cardíaca/terapia , Hipotermia Induzida/efeitos adversos , Estremecimento/efeitos dos fármacos , HumanosRESUMO
BACKGROUND AND PURPOSE: Current literature reports that half of critically ill patients are continued on broad-spectrum antibiotics beyond 72 hours despite no confirmed infection. The purpose of this retrospective study was to identify the incidence of and risk factors for prolonged empiric antimicrobial therapy (PEAT) in adult neurocritical care (NCC) patients treated for pneumonia, hypothesizing that NCC patients will have a higher incidence of PEAT. METHODS: This is a retrospective chart review of adult NCC patients treated for pneumonia. Antibiotic therapy was classified as restrictive, definitive, or PEAT based on culture results and timing of discontinuation or de-escalation. RESULTS: A total of 95 patients (median age: 57 years; 28.4% female; admission diagnosis: 73.7% cerebrovascular, 10.5% neuromuscular, and 15.8% seizure-related) were included in this study. Overall, 59% of antibiotic regimens were considered PEAT, with vancomycin and piperacillin/tazobactam being most commonly prescribed. Median duration of therapy was 6.8 days, with shorter duration in patients with negative culture results compared to those with positive culture results (6.1 days [interquartile range, IQR 4.0-8.3] vs 7.2 days [IQR 5.8-10.3], P < .05). On multivariable analysis, elevated baseline white blood cell count, meeting Centers for Disease Control criteria for pneumonia, and negative bacterial culture were significantly associated with PEAT. CONCLUSION: The incidence of prolonged empiric antibiotic use was high in the NCC population. Patients are at particular risk for PEAT if they have negative cultures. All but one patient did not meet criteria for central fever, highlighting the challenges in identifying fever etiology in the NCC population.
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Lacosamide is a new-generation antiepileptic drug (AED) that is eliminated by both hepatic and renal mechanisms. Lacosamide elimination by continuous renal replacement therapy (CRRT) has never been studied. The objective of this case report was to describe lacosamide pharmacokinetics in the setting of CRRT. We describe a single patient admitted to the study center with status epilepticus and multiorgan failure. The patient required both continuous venovenous hemofiltration (CVVH) and several AEDs. He was receiving intravenous lacosamide 200 mg twice/day at steady state prior to sampling. Plasma lacosamide concentrations were derived using a validated high-performance liquid chromatography method. Parameters were calculated using Phoenix WinNonlin 7.1 software. The peak concentration at steady state was 7.7 mg/L, the trough concentration was 5.9 mg/L (goal 5-12 mg/L). The volume of distribution was 0.7 L/kg, the elimination half-life was 21 hours, and the sieving coefficient was 0.8 (± 0.06). Lacosamide was cleared by CVVH as demonstrated by the sieving coefficient, but plasma concentrations remained within goal range throughout the dosing interval. These results may suggest that lacosamide 200 mg twice/day is a useful dosing strategy for critically ill patients who require CVVH.
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Anticonvulsivantes/sangue , Estado Terminal/terapia , Hemofiltração/tendências , Lacosamida/sangue , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/uso terapêutico , Humanos , Lacosamida/farmacocinética , Lacosamida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estado Epiléptico/sangue , Estado Epiléptico/tratamento farmacológicoRESUMO
OBJECTIVE: To evaluate the quality of available evidence of drug class combinations and their association with the development of acute kidney injury (AKI). DATA SOURCES: A search of MEDLINE and Embase databases was completed using the following terms: "risk factor AND (acute kidney injury or acute kidney failure) AND (drug or medication)." STUDY SELECTION AND DATA EXTRACTION: Inclusion criteria were the following: English language, full-text availability, and at least 1 drug-combination. Each citation was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria. The literature was evaluated using the quality of evidence component of GRADE. No standardized definition of AKI was applied throughout.. DATA SYNTHESIS: Out of 2139 total citations, 151 were assessed for full-text review, with 121 citations (6%) meeting inclusion criteria, producing76 unique drug class combinations. Overall, 56 combinations (73.7%) were considered very low quality; 12 (15.8%) were considered low quality. There were 8 (10.5%) of moderate quality, and no combination was considered high quality. 58 (76%) combinations that had a single citation,with a mean of 1.6 citations per drug class combination. The combination of nonsteroidal anti-inflammatory drugs (NSAIDs) and diuretics was reported in 10 citations, the largest number of citations. CONCLUSIONS: Our study demonstrates a lack of well-designed studies addressing drug class combination-associated AKI. The combination of NSAIDs and diuretics with or without additional renin-angiotensin aldosterone agents had the strongest level of evidence. Despite limitations, the information included in this review may result in additional scrutiny about combining certain individual nephrotoxic drugs.
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Injúria Renal Aguda/induzido quimicamente , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/administração & dosagem , Quimioterapia Combinada , HumanosRESUMO
BACKGROUND: Adjunctive medications to manage alcohol withdrawal syndrome (AWS) in patients not adequately responding to escalating doses of benzodiazepines (BZDs) are limited. The use of the N-methyl-d-aspartate antagonist ketamine, may serve as an effective adjunct agent; however, no published data currently exist for this practice. OBJECTIVE: To determine the safety and efficacy of adjunct ketamine for management of AWS. METHODS: The study was a retrospective review of adult patients from April 2011 to March 2014 who were administered ketamine specifically for management of AWS. Outcomes included changes in BZD requirements and ketamine-related adverse reactions. RESULTS: Of 235 patients screened, 23 patients met study eligibility. Ketamine was initiated primarily with toxicology consultation for significant BZD requirements or delirium tremens. The mean time to initiation of ketamine from first treatment of AWS, and total duration of therapy were 33.6 and 55.8 hours, respectively. Mean initial infusion dose and median total infusion rate during therapy were 0.21 and 0.20 mg/kg/h, respectively. There was no change in sedation or alcohol withdrawal scores in patients within 6 hours of ketamine initiation. The median change in BZD requirements at 12 and 24 hours post-ketamine initiation were -40.0 and -13.3 mg, respectively. The mean time to AWS resolution was 5.6 days. There was one documented adverse reaction of oversedation, requiring dose reduction. CONCLUSIONS: Ketamine appears to reduce BZD requirements and is well tolerated at low doses. Prospective dose range evaluations in the management of AWS would be helpful in determining its place as an adjunctive agent.