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1.
Int J Cardiol ; 356: 1-5, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35395290

RESUMO

BACKGROUND: Administration of intracoronary (IC) adenosine allows an easily feasible, inexpensive, and more rapid alternative method for fractional flow reserve (FFR). It is common practice in many centers worldwide. Nicardipine is a strong coronary vasodilator but its efficacy and safety for assessing FFR is not established. The purpose of present study was to compare the efficacy and safety of IC nicardipine and adenosine for assessing FFR. METHODS: One hundred and fifty-nine patients with a total of 193 vessels undergoing clinically indicated FFR assessment of intermediate coronary stenoses were included. For the initial assessment of FFR, hyperemia was induced by an IC adenosine. After a washout period of 3 min, FFR was reassessed using 200 µg of IC nicardipine. RESULTS: Hyperemic efficacy among two different stimuli was compared. The mean FFR with IC adenosine was 0.83 ± 0.09 and that with an IC nicardipine was 0.84 ± 0.09. The median FFR with an IC adenosine was 0.83 (0.78-0.91) and that with an IC nicardipine was 0.85 (0.79-0.91) (p-value 0.246). Both FFR values showed an excellent correlation (R2 = 0.982, p < 0.001). Nicardipine produced fewer changes in heart rate, less chest pain and less flushing than adenosine. Transient atrioventricular block occurred in 29 patients with IC adenosine and none with IC nicardipine. CONCLUSIONS: IC bolus injection of nicardipine could be introduced as a safe and practical alternative method of inducing hyperemia during FFR measurements. Compared to IC adenosine, IC nicardipine has a similar hyperemic efficacy and excellent side-effect profile.


Assuntos
Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Hiperemia , Adenosina , Cateterismo Cardíaco , Angiografia Coronária/métodos , Estenose Coronária/diagnóstico , Estenose Coronária/tratamento farmacológico , Vasos Coronários , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Humanos , Hiperemia/induzido quimicamente , Nicardipino/efeitos adversos , Índice de Gravidade de Doença , Vasodilatadores
2.
World J Pediatr Congenit Heart Surg ; 13(3): 341-345, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35446217

RESUMO

OBJECTIVE: The use of nicardipine in congenital cardiac surgery has been guarded given the calcium sensitivity of immature myocardium and paucity of clinical data. Reports of nicardipine use have excluded neonates with single ventricles. The goal of this study was to compare the use of nicardipine and sodium nitroprusside for postoperative blood pressure control in young patients recovering from cardiac surgery. METHODS: All neonates (<30 days) and young infants (31-180 days) who received either sodium nitroprusside or nicardipine as first-line therapy for blood pressure control were retrospectively reviewed. Some patients had multiple index operations and each index operation was counted separately regarding treatment with sodium nitroprusside or nicardipine. RESULTS: A total of 59 patients underwent 70 procedures (24 as neonates and 46 as infants). Nicardipine was administered as initial therapy following 33 procedures (n = 28 patients), and sodium nitroprusside was administered as initial therapy following 37 index procedures (n = 31 patients). The duration of treatment was longer (P = .025) when sodium nitroprusside was the initial treatment. Five (15%) patients that received nicardipine required a second blood pressure management agent, and seven (19%) patients that received sodium nitroprusside required a second agent (P = .66). No adverse events related to titratable antihypertensive therapy were recorded in any treatment group. The use of nicardipine resulted in significant medication cost reduction. Based on average wholesale price, patient costs for sodium nitroprusside use were $182,952 ($5,544/pt), while costs for nicardipine were only $24,960 ($780/pt). CONCLUSIONS: Nicardipine can be safely used as a first-line antihypertensive in infants. The use of nicardipine as initial antihypertensive therapy rather than sodium nitroprusside can lead to a significant reduction in medication costs without jeopardizing clinical outcomes.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Hipertensão , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Análise Custo-Benefício , Humanos , Hipertensão/tratamento farmacológico , Lactente , Recém-Nascido , Nicardipino/efeitos adversos , Nitroprussiato/farmacologia , Nitroprussiato/uso terapêutico , Estudos Retrospectivos
3.
Anal Chim Acta ; 1199: 339567, 2022 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-35227379

RESUMO

Electrically conductive polymer nanomaterials signify a promising class of sensing platforms in the field of electrochemistry, but their applications as electrocatalysts are commonly limited by their poor colloidal stability in aqueous media and large particle sizes. Inspired by biomineralization approaches for integrating nanoscale materials, herein, a gadolinium (Gd)-integrated polypyrrole (PPy) electrocatalyst (namely, BSA@PPy-Gd) was successfully prepared by choosing bovine serum albumin (BSA) as a stabilizer for biomimetic mineralization and polymerization in a "one-step" manner. BSA@PPy-Gd possesses outstanding water dispersibility, nanoscale morphology, and improved electrical conductivity. The electrocatalytic competency of the electrochemical (EC) sensing platform fabricated for the sensitive detection of nicardipine (NCD) was assessed. The synergy of remarkable conductivity, superior active surface area, and electrostatic interactions stimulated by the combination of BSA with the NH group of PPy on BSA@PPy-Gd and Gd increases the fast electron transfer at the analyte-electrode junction. The fabricated EC sensor, BSA@PPy-Gd/glassy carbon electrode (GCE), exhibits a current intensity greater than that of PPy/GCE, BSA/GCE, and bare GCE in terms of peak height at a pH of 7.0 in phosphate buffer solution. The newly fabricated EC sensing platform shows excellent electrocatalytic activities for the electroreduction of NCD in terms of a low detection limit (2 nM), good sensitivity, linear dynamic detection ranges (0.01-575 µM), operational stability, and repeatability and was also tested on rat and human serum specimens.


Assuntos
Polímeros , Pirróis , Animais , Biomimética , Eletrodos , Gadolínio , Nicardipino , Ratos
4.
Stroke ; 53(6): 1993-2005, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35354302

RESUMO

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high mortality and morbidity. We aimed to determine the relative benefits of pharmacological prophylactic treatments in patients with aneurysmal subarachnoid hemorrhage by performing a network meta-analysis of randomized trials. METHODS: We searched Medline, Web of Science, Embase, Scopus, ProQuest, and Cochrane Central to February 2020. Pairs of reviewers independently identified eligible trials, extracted data, and assessed the risk of bias. Eligible trials compared the prophylactic effects of any oral or intravenous medications or intracranial drug-eluting implants to one another or placebo or standard of care in adult hospitalized patients with confirmed aneurysmal subarachnoid hemorrhage. We used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to assess the certainty of the evidence. RESULTS: We included 53 trials enrolling 10 415 patients. Nimodipine likely reduces all-cause mortality compared to placebo (odds ratio [OR],0.73 [95% CI, 0.53-1.00]; moderate certainty; absolute risk reduction (ARR), -3.35%). Nimodipine (OR, 1.46 [95% CI, 1.07-1.99]; high certainty; absolute risk increase, 8.25%) and cilostazol (OR, 3.73 [95% CI, 1.14-12.18]; moderate certainty; absolute risk increase, 23.15%) were the most effective treatments in improving disability at the longest follow-up. Compared to placebo, clazosentan (10 mg/kg; OR, 0.39 [95% CI, 0.22-0.68]; high certainty; ARR, -16.65%), nicardipine (OR, 0.48 [95% CI, 0.24-0.94]; moderate certainty; ARR, -13.70%), fasudil (OR, 0.55 [95% CI, 0.31-0.98]; moderate certainty; ARR, -11.54%), and magnesium (OR, 0.66 [95% CI, 0.46-0.94]; high certainty; ARR, -8.37%) proved most effective in reducing the likelihood of delayed cerebral ischemia. CONCLUSIONS: Nimodipine and cilostazol are likely the most effective treatments in preventing morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage. Clazosentan, nicardipine, fasudil, and magnesium showed beneficial effects on delayed cerebral ischemia and vasospasm but they were not found to reduce mortality or disability. Future trials are warranted to elaborately investigate the prophylactic effects of medications that may improve mortality and long-term functional outcomes, such as cilostazol and clazosentan. REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42019122183.


Assuntos
Isquemia Encefálica , Hemorragia Subaracnóidea , Vasoespasmo Intracraniano , Adulto , Cilostazol/uso terapêutico , Humanos , Magnésio/uso terapêutico , Morbidade , Metanálise em Rede , Nicardipino/uso terapêutico , Nimodipina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Hemorragia Subaracnóidea/complicações , Vasoespasmo Intracraniano/etiologia
5.
Can J Physiol Pharmacol ; 100(4): 291-294, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35213242

RESUMO

To evaluate the effect of two concentrations of intravenous administration of nicardipine hydrochloride on nicardipine-related phlebitis in patients with preeclampsia. A total of 100 preeclampsia patients were administered with nicardipine hydrochloride and divided into the low-concentration (LC) and high-concentration (HC) groups. The incidence and severity of phlebitis, time from treatment to onset of phlebitis, skin temperature, visual analogue scale (VAS) score, induration, and systemic adverse reactions were compared between two groups. The incidence rate of phlebitis in the LC group was 20% (10/50), significantly lower than 42% (21/50) in the HC group (P < 0.05). Ridit Analysis showed that the severity of phlebitis in the LC group was remarkably lower than that in the HC group (P < 0.05). In the LC group, the time from intravenous administration to onset of phlebitis was longer, the average skin temperature was higher, the VAS score was lower, and the indurated area was smaller than those in the HC group (all P < 0.05). Intravenous infusion of nicardipine hydrochloride with constant and low concentration reduces the incidence rate of phlebitis, prolongs the time from treatment to onset of phlebitis, alleviates the severity of phlebitis and pain, maintains skin temperature, and minimizes induration in preeclampsia patients without systemic adverse reactions.


Assuntos
Flebite , Pré-Eclâmpsia , Administração Intravenosa , Humanos , Infusões Intravenosas , Nicardipino/efeitos adversos , Flebite/induzido quimicamente , Flebite/tratamento farmacológico , Flebite/epidemiologia , Pré-Eclâmpsia/tratamento farmacológico , Resultado do Tratamento
6.
Pflugers Arch ; 474(5): 541-551, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35157133

RESUMO

The higher permeability of the venules in jejunal microcirculation to albumin contributes to the increased mesenteric lymph formation. Recently, we demonstrated that water intake induced serotonin release from enterochromaffin cells in rat jejunum, serotonin of which circulated through the portal vein into blood circulation and then increased the mesenteric lymph formation. The mode of action of serotonin remains unclear. Therefore, we aimed to clarify the mechanisms involved in the regulation of the jejunal lymph formation with permeant albumin in in vivo rat experiments. We investigated the effects of intravenous administration of serotonin or water intake on the jejunal-originated lymph volume and the concentration of albumin in the lymph in the presence or absence of L-NAME. The effects of intravenous administration of L-NAME, nicardipine, A23187, and ML-7 on the lymph formation with permeant albumin were also evaluated. Serotonin or water intake significantly increased the mesenteric lymph volume with permeant albumin in the jejunal microcirculation. The serotonin- and water intake-mediated responses were significantly reduced by the pretreatment with intravenous administration of L-NAME. Intravenous administration of L-NAME itself also decreased significantly the jejunal lymph formation. Administration of A23187 and ML-7 significantly reduced the jejunal lymph formation with permeant albumin. In contrast, administration of nicardipine significantly increased the lymph formation. In conclusion, portal venous blood flow- or serotonin-mediated NO release from venular endothelial cells plays physiologically key roles in the lymph formation in rat jejunum via the extrusion of calcium ions and inactivation of MLCK in endothelial cells.


Assuntos
Jejuno , Serotonina , Albuminas , Animais , Calcimicina/farmacologia , Células Endoteliais , NG-Nitroarginina Metil Éster/farmacologia , Nicardipino/farmacologia , Ratos , Serotonina/farmacologia
7.
Neurocrit Care ; 36(1): 71-81, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34292474

RESUMO

BACKGROUND: With the increasing use of magnetic resonance imaging in the assessment of acute intracerebral hemorrhage, diffusion-weighted imaging hyperintense lesions have been recognized to occur at sites remote to the hematoma in up to 40% of patients. We investigated whether blood pressure reduction was associated with diffusion-weighted imaging hyperintense lesions in acute intracerebral hemorrhage and whether such lesions are associated with worse clinical outcomes by analyzing imaging data from a randomized trial. METHODS: We performed exploratory subgroup analyses in an open-label randomized trial that investigated acute blood pressure lowering in 1000 patients with intracerebral hemorrhage between May 2011 and September 2015. Eligible participants were assigned to an intensive systolic blood pressure target of 110-139 mm Hg versus 140-179 mm Hg with the use of intravenous nicardipine. Of these, 171 patients had requisite magnetic resonance imaging sequences for inclusion in these subgroup analyses. The primary outcome was the presence of diffusion-weighted imaging hyperintense lesions. Secondary outcomes included death or disability and serious adverse event at 90 days. RESULTS: Diffusion-weighted imaging hyperintense lesions were present in 25% of patients (mean age 62 years). Hematoma volume > 30 cm3 was an adjusted predictor (adjusted relative risk 2.41, 95% confidence interval 1.00-5.80) of lesion presence. Lesions occurred in 25% of intensively treated patients and 24% of standard treatment patients (relative risk 1.01, 95% confidence interval 0.71-1.43, p = 0.97). Patients with diffusion-weighted imaging hyperintense lesions had similar frequencies of death or disability at 90 days, compared with patients without lesions. CONCLUSIONS: Randomized assignment to intensive acute blood pressure lowering did not result in a greater frequency of diffusion-weighted imaging hyperintense lesion. Alternative mechanisms of diffusion-weighted imaging hyperintense lesion formation other than hemodynamic fluctuations need to be explored. Clinical trial registration ClinicalTrials.gov (Ref. NCT01176565; https://clinicaltrials.gov/ct2/show/NCT01176565 ).


Assuntos
Anti-Hipertensivos , Hemorragia Cerebral , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/fisiologia , Hemorragia Cerebral/complicações , Humanos , Pessoa de Meia-Idade , Nicardipino/uso terapêutico , Resultado do Tratamento
8.
J Neurosurg ; 136(1): 115-124, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34087804

RESUMO

OBJECTIVE: Cerebral vasospasm and delayed cerebral ischemia (DCI) contribute to poor outcome following subarachnoid hemorrhage (SAH). With the paucity of effective treatments, the authors describe their experience with intrathecal (IT) nicardipine for this indication. METHODS: Patients admitted to the Emory University Hospital neuroscience ICU between 2012 and 2017 with nontraumatic SAH, either aneurysmal or idiopathic, were included in the analysis. Using a propensity-score model, this patient cohort was compared to patients in the Subarachnoid Hemorrhage International Trialists (SAHIT) repository who did not receive IT nicardipine. The primary outcome was DCI. Secondary outcomes were long-term functional outcome and adverse events. RESULTS: The analysis included 1351 patients, 422 of whom were diagnosed with cerebral vasospasm and treated with IT nicardipine. When compared with patients with no vasospasm (n = 859), the treated group was significantly younger (mean age 51.1 ± 12.4 years vs 56.7 ± 14.1 years, p < 0.001), had a higher World Federation of Neurosurgical Societies score and modified Fisher grade, and were more likely to undergo clipping of the ruptured aneurysm as compared to endovascular treatment (30.3% vs 11.3%, p < 0.001). Treatment with IT nicardipine decreased the daily mean transcranial Doppler velocities in 77.3% of the treated patients. When compared to patients not receiving IT nicardipine, treatment was not associated with an increased rate of bacterial ventriculitis (3.1% vs 2.7%, p > 0.1), yet higher rates of ventriculoperitoneal shunting were noted (19.9% vs 8.8%, p < 0.01). In a propensity score comparison to the SAHIT database, the odds ratio (OR) to develop DCI with IT nicardipine treatment was 0.61 (95% confidence interval [CI] 0.44-0.84), and the OR to have a favorable functional outcome (modified Rankin Scale score ≤ 2) was 2.17 (95% CI 1.61-2.91). CONCLUSIONS: IT nicardipine was associated with improved outcome and reduced DCI compared with propensity-matched controls. There was an increased need for permanent CSF diversion but no other safety issues. These data should be considered when selecting medications and treatments to study in future randomized controlled clinical trials for SAH.


Assuntos
Bloqueadores dos Canais de Cálcio/administração & dosagem , Bloqueadores dos Canais de Cálcio/uso terapêutico , Nicardipino/administração & dosagem , Nicardipino/uso terapêutico , Hemorragia Subaracnóidea/complicações , Vasoespasmo Intracraniano/tratamento farmacológico , Vasoespasmo Intracraniano/etiologia , Adulto , Fatores Etários , Idoso , Aneurisma Roto , Ruptura Aórtica/complicações , Ruptura Aórtica/cirurgia , Bloqueadores dos Canais de Cálcio/efeitos adversos , Cuidados Críticos , Procedimentos Endovasculares , Feminino , Humanos , Injeções Espinhais , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Nicardipino/efeitos adversos , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento
9.
Am J Health Syst Pharm ; 79(9): e110-e116, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-34636881

RESUMO

PURPOSE: To compare pharmacy-prepared nicardipine and premade clevidipine with regard to time to goal systolic blood pressure (SBP) in acute cerebrovascular accident (CVA). METHODS: A retrospective, observational study was conducted comparing patients with acute CVA who received nicardipine or clevidipine. The primary objective was time to goal SBP. Secondary objectives included time from order to administration, time from administration to goal SBP, percentage of SBP readings below goal, total volume administered, hospital and intensive care unit lengths of stay, inpatient mortality and adverse events. RESULTS: Seventy-one patients were included in the study, 37 in the nicardipine group and 34 in the clevidipine group. A significant difference was found in mean time to goal SBP (150.9 minutes in the nicardipine group vs 69.3 minutes in the clevidipine group, P < 0.01). Time from order to administration was 80.1 minutes in the nicardipine group and 35.2 minutes in the clevidipine group (P < 0.01). Mean time from administration to goal SBP was 70.9 minutes in the nicardipine group and 42.3 minutes in the clevidipine group (P = 0.02). There was no difference between groups in percentage of SBP readings below goal, total volume administered, length of stay, or inpatient mortality. Adverse events occurred in 13 (35.1%) of the nicardipine-treated patients and 17 (50%) of the clevidipine-treated patients (P = 0.42). CONCLUSION: Compared to use of pharmacy-prepared nicardipine, use of premade clevidipine was associated with a shorter time to goal SBP in patients with acute CVA. There were no significant between-group differences in safety outcomes. Premade clevidipine should be considered over pharmacy-prepared nicardipine when rapid blood pressure lowering is warranted in acute CVA.


Assuntos
Hipertensão , Farmácia , Acidente Vascular Cerebral , Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea , Objetivos , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Nicardipino/efeitos adversos , Piridinas , Estudos Retrospectivos , Acidente Vascular Cerebral/tratamento farmacológico
10.
Neurocrit Care ; 36(2): 662-681, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34940927

RESUMO

One of the challenges in bringing new therapeutic agents (since nimodipine) in for the treatment of cerebral ischemia associated with aneurysmal subarachnoid hemorrhage (aSAH) is the incongruence in therapeutic benefit observed between phase II and subsequent phase III clinical trials. Therefore, identifying areas for improvement in the methodology and interpretation of results is necessary to increase the value of phase II trials. We performed a systematic review of phase II trials that continued into phase III trials, evaluating a therapeutic agent for the treatment of cerebral ischemia associated with aSAH. We followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines for systematic reviews, and review was based on a peer-reviewed protocol (International Prospective Register of Systematic Reviews no. 222965). A total of nine phase III trials involving 7,088 patients were performed based on eight phase II trials involving 1558 patients. The following therapeutic agents were evaluated in the selected phase II and phase III trials: intravenous tirilazad, intravenous nicardipine, intravenous clazosentan, intravenous magnesium, oral statins, and intraventricular nimodipine. Shortcomings in several design elements of the phase II aSAH trials were identified that may explain the incongruence between phase II and phase III trial results. We suggest the consideration of the following strategies to improve phase II design: increased focus on the selection of surrogate markers of efficacy, selection of the optimal dose and timing of intervention, adjustment for exaggerated estimate of treatment effect in sample size calculations, use of prespecified go/no-go criteria using futility design, use of multicenter design, enrichment of the study population, use of concurrent control or placebo group, and use of innovative trial designs such as seamless phase II to III design. Modifying the design of phase II trials on the basis of lessons learned from previous phase II and phase III trial combinations is necessary to plan more effective phase III trials.


Assuntos
Isquemia Encefálica , Hemorragia Subaracnóidea , Vasoespasmo Intracraniano , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Infarto Cerebral/complicações , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Humanos , Estudos Multicêntricos como Assunto , Nicardipino/uso terapêutico , Nimodipina/uso terapêutico , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/tratamento farmacológico , Resultado do Tratamento , Vasoespasmo Intracraniano/complicações , Vasoespasmo Intracraniano/etiologia
11.
Neurocrit Care ; 36(3): 983-992, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34904214

RESUMO

BACKGROUND: Intracranial hemorrhage is associated with high mortality and morbidity. Lowering systolic blood pressure (SBP) with an intravenous antihypertensive, such as nicardipine or clevidipine, may reduce the risk of hematoma expansion and rebleeding. Previous studies comparing nicardipine and clevidipine in patients with stroke found no significant difference in blood pressure management. The inclusion of patients with ischemic stroke limited those studies because of convoluted results related to faster door-to-needle times. The purpose of this study was to compare clevidipine with nicardipine in time to goal SBP in hemorrhagic stroke. METHODS: This single-center retrospective observational cohort study evaluated adult hemorrhagic patients with stroke who received clevidipine or nicardipine from January 1, 2015, to December 31, 2020. Patients were excluded if they had trauma-related hemorrhage, received concurrent continuous intravenous antihypertensives, received the study drug for less than 1-h duration, had a less than 24-h washout period between agents, required any dialysis, were pregnant, or were incarcerated. The primary outcome was time to goal SBP. Secondary outcomes included need for additional antihypertensives, percentage of time at goal SBP, all-cause mortality, 30-day readmission, rebleeding, total volume of antihypertensive infusion, hematoma expansion, intensive care unit length of stay (LOS), hospital LOS, and cost of infusion. Safety outcomes included hypotension, severe hypotension, rebound hypertension, bradycardia, tachycardia, onset of atrial fibrillation, and acute kidney injury. RESULTS: Of 89 patients included in this study, 60 received nicardipine and 29 received clevidipine. There was no significant difference between nicardipine and clevidipine in time to goal SBP in the unmatched cohort (30 vs. 45 min; p = 0.73) or the propensity-score-matched cohort (30 vs. 45 min; p = 0.47). Results were not affected by potential confounders in the multiple linear regression. The nicardipine group had a higher total volume from infusion compared with the clevidipine group (1410 vs. 330 mL; p < 0.0001) but significantly lower cost ($99.6 vs. $497.4; p < 0.0001). There were no significant differences in need for additional antihypertensives, percentage of time at goal SBP, all-cause mortality, 30-day readmission, rebleeding, hematoma expansion, intensive care unit LOS, and hospital LOS. Compared with the clevidipine group, the nicardipine group had less rebound hypertension (40% vs. 75.9%; p = 0.0017) and less bradycardia (23.3% vs. 44.8%; p = 0.05). There were no significant differences in hypotension, severe hypotension, tachycardia, and acute kidney injury. CONCLUSIONS: In patients with hemorrhagic stroke, nicardipine appeared to have similar efficacy as clevidipine in SBP reduction, with a more likely reduction of rebound hypertension and drug cost. This retrospective study was underpowered, which may limit these implications. Further prospective studies are warranted to confirm these results.


Assuntos
Injúria Renal Aguda , AVC Hemorrágico , Hipertensão , Hipotensão , Acidente Vascular Cerebral , Adulto , Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea/fisiologia , Bradicardia , Hematoma/complicações , Humanos , Hipotensão/tratamento farmacológico , Nicardipino/farmacologia , Nicardipino/uso terapêutico , Piridinas , Estudos Retrospectivos , Resultado do Tratamento
12.
Medicine (Baltimore) ; 100(31): e26837, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397851

RESUMO

INTRODUCTION: Moyamoya disease (MMD) and posterior reversible encephalopathy syndrome (PRES) share similar pathophysiological characteristics of endothelial dysfunction and impaired cerebral autoregulation. However, there have never been any published studies to demonstrate the relationship between these 2 rare diseases. PATIENT CONCERNS: A 26-year-old Asian man presented with a throbbing headache, blurred vision, and extremely high blood pressure. We initially suspected acute cerebral infarction based on the cerebral computed tomography, underlying MMD, and prior ischemic stroke. However, the neurological symptoms deteriorated progressively. DIAGNOSIS: Cerebral magnetic resonance imaging indicated the presence of vasogenic edema rather than cerebral infarction. INTERVENTIONS AND OUTCOMES: An appropriate blood pressure management prevents the patient from disastrous outcomes successfully. Cerebral magnetic resonance imaging at 2 months post treatment disclosed the complete resolution of cerebral edema. The patient's recovery from clinical symptoms and the neuroimaging changes supported the PRES diagnosis. CONCLUSION: This report suggests that patients with MMD may be susceptible to PRES. It highlights the importance of considering PRES as a differential diagnosis while providing care to MMD patients with concurrent acute neurological symptoms and a prompt intervention contributes to a favorable clinical prognosis.


Assuntos
Edema Encefálico , Hipertensão , Doença de Moyamoya , Nicardipino/administração & dosagem , Síndrome da Leucoencefalopatia Posterior , Adulto , Anti-Hipertensivos/administração & dosagem , Encéfalo/diagnóstico por imagem , Edema Encefálico/diagnóstico por imagem , Edema Encefálico/etiologia , Edema Encefálico/terapia , Diagnóstico Diferencial , Humanos , Hipertensão/diagnóstico , Hipertensão/etiologia , Hipertensão/terapia , Imageamento por Ressonância Magnética/métodos , Masculino , Doença de Moyamoya/complicações , Doença de Moyamoya/diagnóstico , Doença de Moyamoya/fisiopatologia , Doença de Moyamoya/terapia , Exame Neurológico/métodos , Síndrome da Leucoencefalopatia Posterior/complicações , Síndrome da Leucoencefalopatia Posterior/diagnóstico , Síndrome da Leucoencefalopatia Posterior/fisiopatologia , Síndrome da Leucoencefalopatia Posterior/terapia , Prognóstico , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
13.
World Neurosurg ; 155: 41-53, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34339892

RESUMO

BACKGROUND: Vasospasm and delayed ischemic neurologic deficits are the leading causes of morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). Several therapeutic agents have been assessed in randomized controlled trials for their efficacy in reducing the incidence of vasospasm and improving functional outcome. The aim of this network meta-analysis is to compare all these therapeutic agents for their effect on functional outcome and other parameters after aSAH. METHODS: A comprehensive search of different databases was performed to retrieve randomized controlled trials describing the effect of various therapeutic approaches on functional outcome and other parameters after aSAH. RESULTS: Ninety-two articles were selected for full text review and 57 articles were selected for the final analysis. Nicardipine prolonged-release implants were found to be the best treatment in terms of favorable outcome (odds ratio [OR], 8.55; 95% credible interval [CrI], 1.63-56.71), decreasing mortality (OR, 0.08; 95% CrI, 0-0.82), and preventing angiographic vasospasm (OR, 0.018; 95% CrI, 0.00057-0.16). Cilostazol was found to be the second-best treatment in improving favorable outcomes (OR, 3.58; 95% CrI, 1.97-6.57) and decreasing mortality (OR, 0.41; 95% CrI, 0.12-1.15). Fasudil (OR, 0.16; 95% CrI, 0.03-0.78) was found to be the best treatment in decreasing increased vessel velocity and enoxaparin (OR, 0.25; 95% CrI, 0.057-1.0) in preventing delayed ischemic neurologic deficits. CONCLUSIONS: Our analysis showed that nicardipine prolonged-release implants and cilostazol were associated with the best chance of improving favorable outcome and mortality in patients with aSAH. However, larger multicentric studies from other parts of the world are required to confirm these findings.


Assuntos
Cilostazol/administração & dosagem , Nicardipino/administração & dosagem , Recuperação de Função Fisiológica/efeitos dos fármacos , Hemorragia Subaracnóidea/tratamento farmacológico , Vasodilatadores/administração & dosagem , Vasoespasmo Intracraniano/tratamento farmacológico , Preparações de Ação Retardada/administração & dosagem , Humanos , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Recuperação de Função Fisiológica/fisiologia , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/fisiopatologia , Resultado do Tratamento , Vasoespasmo Intracraniano/etiologia , Vasoespasmo Intracraniano/fisiopatologia
14.
J Stroke Cerebrovasc Dis ; 30(10): 106020, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34365121

RESUMO

OBJECTIVES: A paucity of treatments to prevent delayed cerebral ischemia (DCI) has stymied recovery after aneurysmal subarachnoid hemorrhage (aSAH). Nicardipine has long been recognized as a potent cerebrovascular vasodilator with a history off-label use to prevent vasospasm and DCI. Multiple centers have developed nicardipine prolonged release implants (NPRI) that are directly applied during clip ligation to locally deliver nicardipine throughout the vasospasm window. Here we perform a systematic review and meta-analysis to assess whether NPRI confers protection against DCI and improves functional outcomes after aSAH. MATERIALS AND METHODS: A systematic search of PubMed, Ovid Embase, and Cochrane databases was performed for studies reporting the use of NPRI after aSAH published after January 1, 1980. We included all studies assessing the association of NPRI with DCI and or functional outcomes. Findings from studies with control arms were analyzed using a random effects model. A separate network meta-analysis was performed, including controlled NPRI studies, single-arm NPRI reports, and the control-arms of modern aSAH randomized clinical trials as additional comparators. RESULTS: The search identified 214 unique citations. Three studies with 284 patients met criteria for the random effects model. The pooled summary odds ratio for the association of NPRI and DCI was 0.21 (95% CI 0.09-0.49, p = 0.0002) with no difference in functional outcomes (OR 1.80, 95% CI 0.63 - 5.16, p = 0.28). 10 studies of 866 patients met criteria for the network meta-analysis. The pooled summary odds ratio for the association of NPRI and DCI was 0.30 (95% CI 0.13-0.89,p = 0.017) with a trend towards improved functional outcomes (OR 1.68, 0.63 - 4.13 95% CI, p = 0.101). CONCLUSIONS: In these meta-analyses, NPRI decreases the incidence of DCI with a non-significant trend towards improvement in functional outcomes. Randomized trials on the role of intrathecal calcium channel blockers are warranted to evaluate these observations in a prospective manner.


Assuntos
Isquemia Encefálica/prevenção & controle , Nicardipino/administração & dosagem , Hemorragia Subaracnóidea/tratamento farmacológico , Vasodilatadores/administração & dosagem , Vasoespasmo Intracraniano/prevenção & controle , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/fisiopatologia , Implantes de Medicamento , Humanos , Incidência , Metanálise em Rede , Nicardipino/efeitos adversos , Recuperação de Função Fisiológica , Fatores de Risco , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/epidemiologia , Hemorragia Subaracnóidea/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Vasodilatadores/efeitos adversos , Vasoespasmo Intracraniano/diagnóstico por imagem , Vasoespasmo Intracraniano/epidemiologia , Vasoespasmo Intracraniano/fisiopatologia
15.
Neurology ; 97(9): e913-e921, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34210824

RESUMO

BACKGROUND AND OBJECTIVE: The clinical effect of renal impairment on intracerebral hemorrhage (ICH) is unknown. This study sought to assess whether estimated glomerular filtration rate (eGFR) affects clinical outcomes or modifies the efficacy of intensive systolic blood pressure (BP) control (target, 110-139 mm Hg) against the standard (target, 140-179 mm Hg) among patients with ICH. METHODS: We conducted post hoc analyses of ATACH-2, a randomized, 2-group, open-label trial. The baseline eGFR of each eligible patient was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. The outcome of interest was death or disability at 90 days. Multivariate logistic regression models were used for analysis. RESULTS: Among the 1,000 patients randomized, 974 were analyzed. The median baseline eGFR was 88 (interquartile range, 68, 99) mL/min/1.73 m2; 451 (46.3%), 363 (37.3%), and 160 (16.4%) patients had baseline eGFR values of ≥90, 60-89, and <60 mL/min/1.73 m2, respectively. Compared with normal eGFR (≥90 mL/min/1.73 m2), higher odds of death or disability were noted among those with eGFR values of <60 mL/min/1.73 m2 (adjusted odds ratio [OR], 2.02; 95% confidence interval [CI], 1.25-3.26) but not among those with eGFR values of 60-89 mL/min/1.73 m2 (OR, 1.01; 95% CI, 0.70-1.46). The odds of death or disability were significantly higher in the intensive arm among patients with decreased eGFR; the ORs were 0.89 (95% CI, 0.55-1.44), 1.13 (0.68-1.89), and 3.60 (1.47-8.80) in patients with eGFR values of ≥90, 60-89, and <60 mL/min/1.73 m2, respectively (p for interaction = 0.02). DISCUSSION: Decreased eGFR is associated with unfavorable outcomes following ICH. The statistically significant interaction between the eGFR group and treatment assignment raised safety concerns for the intensive BP-lowering therapy among patients with renal impairment. TRIAL REGISTRATION INFORMATION: Clinicaltrials.gov identifier: NCT01176565. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in spontaneous ICH, decreased eGFR identifies patients at risk of death or disability following intensive BP control.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hemorragia Cerebral/complicações , Hemorragia Cerebral/tratamento farmacológico , Nicardipino/uso terapêutico , Insuficiência Renal/complicações , Idoso , Pressão Sanguínea/efeitos dos fármacos , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
16.
J Stroke Cerebrovasc Dis ; 30(9): 105959, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34217067

RESUMO

PURPOSE: To assess the safety and efficacy of continuous infusion (CIV)-labetalol compared to -nicardipine in controlling blood pressure (BP) in the acute stroke setting. MATERIALS: Patients were eligible if they had a diagnosis of an acute stroke and were administered either CIV-labetalol or CIV-nicardipine. Study outcomes were assessed within the first 24 h of the antihypertensive infusion. RESULTS: A total of 3,093 patients were included with 3,008 patients in the CIV-nicardipine group and 85 in the CIV-labetalol group. No significant difference was observed in percent time at goal BP between the nicardipine (82%) and labetalol (85%) groups (p = 0.351). There was also no difference in BP variability between nicardipine (37%) and labetalol (39%) groups (p = 0.433). Labetalol was found to have a shorter time to goal BP as compared to nicardipine (24 min vs. 40 min; p = 0.021). While CIV-nicardipine did have a higher incidence of tachycardia compared to labetalol (17% vs. 4%; p <0.001), the incidence of hypotension (13% vs. 15%; p = 0.620) and bradycardia (24% vs. 22%; p = 0.797) were similar. CONCLUSIONS: These results indicate that CIV-labetalol and CIV-nicardipine are comparable in safety and efficacy in controlling BP for patients with acute stroke.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/administração & dosagem , Hipertensão/tratamento farmacológico , Labetalol/administração & dosagem , Nicardipino/administração & dosagem , Acidente Vascular Cerebral/complicações , Antagonistas de Receptores Adrenérgicos alfa 1/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/efeitos adversos , Bradicardia/induzido quimicamente , Bradicardia/fisiopatologia , Bloqueadores dos Canais de Cálcio/efeitos adversos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/diagnóstico , Hipertensão/etiologia , Hipertensão/fisiopatologia , Hipotensão/induzido quimicamente , Hipotensão/fisiopatologia , Infusões Intravenosas , Labetalol/efeitos adversos , Masculino , Pessoa de Meia-Idade , Nicardipino/efeitos adversos , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico , Fatores de Tempo , Resultado do Tratamento , Estados Unidos
17.
Neurology ; 97(8): e755-e764, 2021 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34144995

RESUMO

OBJECTIVE: Hematoma expansion (HE) is commonly analyzed as a dichotomous outcome in intracerebral hemorrhage (ICH) trials. In this proof-of-concept study, we propose an HE shift analysis model as a method to improve the evaluation of candidate ICH therapies. METHODS: Using data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-2) trial, we performed HE shift analysis in response to intensive blood pressure lowering by generating polychotomous strata based on previously established HE definitions, percentile/absolute quartiles of hematoma volume change, and quartiles of 24-hour follow-up hematoma volumes. The relationship between blood pressure treatment and HE shift was explored with proportional odds models. RESULTS: The primary analysis population included 863 patients. In both treatment groups, approximately one-third of patients exhibited no HE. With the use of a trichotomous HE stratification, the highest strata of ≥33% revealed a 5.8% reduction in hematoma growth for those randomized to intensive therapy (adjusted odds ratio [aOR] 0.77, 95% confidence interval [CI] 0.60-0.99). Using percentile quartiles of hematoma volume change, we observed a favorable shift to reduce growth in patients treated with intensive therapy (aOR 0.73, 95% CI 0.57-0.93). Similarly, in a tetrachotomous analysis of 24-hour follow-up hematoma volumes, shifts in the highest stratum (>21.9 mL) were most notable. CONCLUSIONS: Our findings suggest that intensive blood pressure reduction may preferentially mitigate growth in patients at risk of high volume HE. A shift analysis model of HE provides additional insights into the biological effects of a given therapy and may be an additional way to assess hemostatic agents in future studies. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier:NCT01176565.


Assuntos
Anti-Hipertensivos/administração & dosagem , Hemorragia Cerebral/tratamento farmacológico , Hemorragia Cerebral/patologia , Hematoma/tratamento farmacológico , Hematoma/patologia , Nicardipino/administração & dosagem , Avaliação de Processos e Resultados em Cuidados de Saúde , Doença Aguda , Idoso , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral Intraventricular/diagnóstico por imagem , Hemorragia Cerebral Intraventricular/patologia , Progressão da Doença , Feminino , Hematoma/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudo de Prova de Conceito , Estudos Prospectivos
18.
Physiol Res ; 70(3): 437-446, 2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-33982580

RESUMO

Gastrointestinal motility was disturbed in W/Wv, which were lacking of interstitial cells of Cajal (ICC). In this study, we have investigated the role of arecoline hydrobromide (AH) on smooth muscle motility in the jejunum of W/Wv and wild-type (WT) mice. The jejunum tension was recorded by an isometric force transducer. Intracellular recording was used to identify whether AH affects slow wave and resting membrane potential (RMP) in vitro. The whole-cell patch clamp technique was used to explore the effects of AH on voltage-dependent potassium channels for jejunum smooth muscle cells. AH enhanced W/Wv and WT jejunum contractility in a dose-dependent manner. Atropine and nicardipine completely blocked the excitatory effect of AH in both W/Wv and WT. TEA did not reduce the effect of AH in WT, but was sufficient to block the excitatory effect of AH in W/Wv. AH significantly depolarized the RMP of jejunum cells in W/Wv and WT. After pretreatment with TEA, the RMP of jejunum cells indicated depolarization in W/Wv and WT, but subsequently perfused AH had no additional effect on RMP. AH inhibited the voltage-dependent K+ currents of acutely isolated mouse jejunum smooth muscle cells. Our study demonstrate that AH enhances the contraction activity of jejunum smooth muscle, an effect which is mediated by voltage-dependent potassium channels that acts to enhance the excitability of jejunum smooth muscle cells in mice.


Assuntos
Arecolina/farmacologia , Jejuno/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Canais de Potássio de Abertura Dependente da Tensão da Membrana/efeitos dos fármacos , Animais , Atropina/farmacologia , Relação Dose-Resposta a Droga , Motilidade Gastrointestinal/efeitos dos fármacos , Camundongos , Contração Muscular/efeitos dos fármacos , Nicardipino/farmacologia , Técnicas de Patch-Clamp , Bloqueadores dos Canais de Potássio/farmacologia
19.
Clin Neurol Neurosurg ; 206: 106705, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34053805

RESUMO

Reversible cerebral vasoconstriction syndrome (RCVS) presents with a thunderclap headache, often prompting brain imaging. Most patients fully recover with supportive care and time, but oral calcium channel blockers are often used in patients with severe vasoconstriction. In this case report, we present a patient with severe vasoconstriction leading to weakness refractory to oral calcium channel blockers. Intrathecal nicardipine was administered via an external ventricular drain and the patient subsequently showed improvement of her weakness and significant improvement of vasospasm on Computed Tomography Angiography. We suggest further studies to determine the efficacy of intrathecal nicardipine in patients with RCVS not responsive to oral calcium channel blockers.


Assuntos
Nicardipino/administração & dosagem , Vasodilatadores/administração & dosagem , Vasoespasmo Intracraniano/tratamento farmacológico , Adulto , Feminino , Transtornos da Cefaleia Primários/etiologia , Humanos , Injeções Espinhais , Síndrome , Vasoespasmo Intracraniano/complicações
20.
J Atheroscler Thromb ; 28(12): 1340-1348, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33746145

RESUMO

AIM: The cardio-ankle vascular index (CAVI) consists of intrinsic and functional arterial stiffness mainly regulated by vasoactive compounds. A new stiffness index of the aorta (aBeta) and iliac-femoral arteries (ifBeta) was determined by applying the CAVI theory to the whole aorta and iliac-femoral arteries. We investigated the changes in aBeta and ifBeta in response to decreased blood pressure (BP) induced by the Ca2+ channel blocker nicardipine to elucidate the involvement of Ca2+ in aBeta and ifBeta. METHODS: Pressure waves at the origin of the aorta (oA), distal end of the abdominal aorta (dA), and left femoral artery (fA) as well as flow waves at the oA were simultaneously recorded before and after the infusion of nicardipine (50 µg/kg/min) for 2 min in 12 male rabbits under pentobarbital anesthesia. Beta was calculated using the following formula: Beta=2ρ / PP×ln (SBP / DBP)×PWV2, where ρ, SBP, DBP, and PP denote blood density and systolic, diastolic, and pulse pressures, respectively. aBeta, ifBeta, and aortic-iliac-femoral Beta (aifBeta) were calculated using aPWV, ifPWV, and aifPWV, respectively. RESULTS: SBP, mean arterial pressure (MAP), DBP, and total peripheral vascular resistance significantly decreased during the administration of nicardipine, whereas cardiac output significantly increased. aBeta and ifBeta significantly increased and decreased, respectively, whereas aifBeta did not change despite the decrease in BP. ifBeta and aBeta positively and negatively correlated with BP, respectively, whereas aifBeta did not correlate with SBP. CONCLUSIONS: There were contradictory arterial responses to nicardipine between the elastic and muscular arteries. Unknown vasoconstriction mechanisms that are not involved in Ca2+ influx may function in the aorta in response to decreased BP.


Assuntos
Aorta Abdominal/fisiopatologia , Artéria Femoral/fisiopatologia , Artéria Ilíaca/fisiopatologia , Nicardipino/farmacologia , Rigidez Vascular/efeitos dos fármacos , Animais , Pressão Arterial/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/farmacologia , Índice Vascular Coração-Tornozelo , Análise de Onda de Pulso/métodos , Coelhos , Resistência Vascular/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacos , Vasoconstrição/fisiologia
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