Search

Objective: Optimal blood pressure (BP) control in acute intracerebral hemorrhage (ICH) remains controversial. We determined the effects of SBP lowering to 160 mmHg or more using intravenous nicardipine for acute ICH patients., Methods: This is a prospective, multicenter, observational study conducted in Japan, with the lack of control groups. Patients with supratentorial ICH within 3 h of onset, admission SBP 180 mmHg or more, Glasgow Coma Scale (GCS) 5 or more, and hematoma volume less than 60 ml were initially treated with intravenous nicardipine to maintain SBP between 120 and 160 mmHg with 24-h frequent BP monitoring. The primary endpoints were neurological deterioration within 72 h [GCS decrement ≥ 2 points or National Institutes of Health Stroke Scale (NIHSS) increment ≥ 4 points; estimated 90% confidence interval (CI) on the basis of previous studies: 15.2-25.9%] and serious adverse effects (SAE) to stopping intravenous nicardipine within 24 h (1.8-8.9%). The secondary endpoints included hematoma expansion more than 33% at 24 h (17.1-28.3%), modified Rankin Scale (mRS) 4 or more (54.5-67.9%) and death at 3 months (6.0-13.5%)., Results: We enrolled 211 Japanese patients (81 women, 65.6 ± 12.0 years old). At baseline, BP was 201.8 ± 15.7/107.9 ± 15.0 mmHg. Median hematoma volume was 10.2 ml (interquartile range 5.6-19.2), and NIHSS score was 13 (8-17). Neurological deterioration was identified in 17 patients (8.1%), SAE in two (0.9%), hematoma expansion in 36 (17.1%), mRS 4 or more in 87 (41.2%), and death in four (1.9%). All the results were equal to or below the estimated lower 90% CI., Conclusion: SBP lowering to 160 mmHg or less using nicardipine appears to be well tolerated and feasible for acute ICH.

Background: Critically ill patients with acute hypertension often require titratable rapid blood pressure (BP) reductions using parenteral administration of drugs. There are few comparative studies available to make informed drug product selection decisions. The purpose of this study was to evaluate the short-term clinical outcomes and costs of intravenous labetalol or intravenous nicardipine in the management of hypertension in critically ill patients., Methods: This study was a retrospective analysis of consecutive patients receiving intravenous labetalol or intravenous nicardipine in the intensive care unit with acute elevations in either systolic (>160 mm Hg) or diastolic (>90 mm Hg) BP. Patient demographics, clinical characteristics, and short-term clinical outcomes were abstracted from the medical record. Hospital costs were calculated from hospital billing forms., Results: A total of 189 patients receiving labetalol and 193 patients receiving nicardipine were included in the analysis. The average hourly dose was 37.3 ± 9.4 mg/h for labetalol compared with 7.1 ± 5.6 mg/h for nicardipine (P < .001). The average total dose of labetalol was 170.9 ± 32.6 mg compared with 112.2 ± 29.1 mg for nicardipine (P = .02). The duration of therapy was significantly shorter for labetalol (8.2 ± 6.2 hours) compared with nicardipine (15.8 ± 4.4 hours) (P = .03). There were a greater number of dose titrations with labetalol (6.1 ± 6.2) than with nicardipine (4.7 ± 4.9), but this difference was not significantly different (P = .29). There were no significant differences in the magnitude of the average change in systolic (P = .79) or diastolic (P = .82) BP between labetalol and nicardipine. The proportion of patients achieving their BP targets was significantly greater with nicardipine (83%) than with labetalol (67%) (P = .04). The proportion of patients requiring an alternate antihypertensive agent was significantly greater with labetalol than with nicardipine (31% vs 17%; P = .02). The total number of all-cause adverse events was significantly greater with labetalol (61%) than with nicardipine (48%) (P = .04). Labetalol was associated with a significantly greater incidence of hypotension and bradycardia or atrioventricular block compared with nicardipine. There was no significant difference in the frequency of other adverse events between these 2 drugs. The median hospital costs were not significantly different between patients receiving labetalol and patients receiving nicardipine., Conclusion: Our study suggests that nicardipine is a more effective antihypertensive agent than labetalol in an unselected group of patients who develop hypertension in the intensive care unit setting. A major advantage of nicardipine compared with labetalol was fewer adverse effects. Nicardipine was associated with less hypotension and bradycardia or atrioventricular block, resulting in a lower rate of drug discontinuation compared with labetalol., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The authors performed a multicenter prospective study to evaluate the feasibility and safety of intravenous nicardipine hydrochloride for acute hypertension in patients with intracerebral hemorrhage (ICH). This study included 88 patients (mean age: 58.3 yr, range 26-87 yr) with ICH and acute hypertension in 5 medical centers between August 2008 and November 2010, who were treated using intravenous nicardipine. Administration of nicardipine resulted in a decrease from mean systolic blood pressure (BP) (175.4 ± 33.7 mmHg) and diastolic BP (100.8 ± 22 mmHg) at admission to mean systolic BP (127.4 ± 16.7 mmHg) and diastolic BP (67.2 ± 12.9 mmHg) in 6 hr after infusion (P < 0.001, mixed-effect linear models). Among patients who underwent follow-up by computed tomography, hematoma expansion at 24 hr (more than 33% increase in hematoma size at 24 hr) was observed in 3 (3.4%) of 88 patients. Neurological deterioration (defined as a decrease in initial Glasgow coma scale ≥ 2) was observed in 2 (2.2%) of 88 patients during the treatment. Aggressive nicardipine treatment of acute hypertension in patients with ICH can be safe and effective with a low rate of neurological deterioration and hematoma expansion.

Background: Coronary endothelial shear stress (ESS) triggered the development of atherosclerosis. However, the effect of calcium channel antagonist on the distribution of ESS remained unclear., Methods: Twenty consecutive patients with acute coronary syndrome (ACS) 48 hours after maximal medication with single left anterior descending artery stenosis < 50% were studied. Nicardipine was intravenously injected at 1 µg/kg after a bolus of 10 mg in order to achieve mean blood pressure (MBP) reduced by 10% or more, or the heart rate increased by 10 - 15 beats/min. Hemodynamic variables and angiogram at baseline and during injection of nicardipine were recorded, respectively. Coronary artery 3-D reconstruction was used for the analysis of ESS., Results: Distal reference-vessel-diameter and minimal lumen diameter decreased significantly from (2.42 ± 0.41) mm and (1.47 ± 0.49) mm at baseline to (2.22 ± 0.35) mm and (1.35 ± 0.49) mm at maximal drug-dosage (P = 0.018 and 0.020, respectively). Nicardipine did not change blood velocity. Lowest mean shear stress at segments 2-mm distal to plaque increased significantly from (0.034 ± 0.519) Pa at baseline to (0.603 ± 0.728) Pa (P = 0.013) at peak effect of drug., Conclusions: Nicardipine was associated with the constriction of diseased vessel segment that adapted to the reduction of blood pressure, without dynamic change of blood velocity at each stage of whole cardiac cycle. Increased ESS value at segments distal to plaque reflected the cardioprotection by nicardipine (ChiCTR-TRC-10000964).

Hypertensive emergencies are acute elevations in blood pressure (BP) that occur in the presence of progressive end-organ damage. Hypertensive urgencies, defined as elevated BP without acute end-organ damage, can often be treated with oral agents, whereas hypertensive emergencies are best treated with intravenous titratable agents. However, a lack of head-to-head studies has made it difficult to establish which intravenous drug is most effective in treating hypertensive crises. This systematic review presents a synthesis of published studies that compare the antihypertensive agents nicardipine and labetalol in patients experiencing acute hypertensive crises. A MEDLINE search was conducted using the term "labetalol AND nicardipine AND hypertension." Conference abstracts were searched manually. Ultimately, 10 studies were included, encompassing patients with hypertensive crises across an array of indications and practice environments (stroke, the emergency department, critical care, surgery, pediatrics, and pregnancy). The results of this systematic review show comparable efficacy and safety for nicardipine and labetalol, although nicardipine appears to provide more predictable and consistent BP control than labetalol., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: This study aimed to compare the acute effects of nicardipine and esmolol on hemodynamic and endothelial shear stress (ESS) in patients with unstable angina (UA) and moderate coronary stenosis (MCS)., Background: Nicardipine and esmolol exhibit cardioprotection via different mechanisms. However, their acute effects on hemodynamic and ESS are still unknown., Methods: One-hundred sixteen patients with UA and MSC were randomly divided into nicardipine (n = 59) and esmolol (n = 57) groups. Drugs were injected as a bolus followed by continuous infusion to achieve the steady states defined as the mean blood pressure (MBP) reduced by ≥ 10% or a heart-rate change by ≥ 15 bpm, lasting for at least 10 min. The aortic pressure (AP), EKG, blood velocity, right atrial pressure, distal coronary pressure (DCP), systolic time (ST), isovolumetric diastolic time (IVDT), speed filling time (SFT), and ESS were simultaneously calculated at baseline and steady states., Results: Both drugs significantly reduced blood pressure and rate-pressure load. Infusion of nicardipine was associated with negative remodeling of the distal segment (P= 0.005). Esmolol, rather than nicardipine, increased minimal lumen diameter (P= 0.040), prolonged SFT (0.34 ± 0.03 s vs. 0.41 ± 0.03 s, P < 0.001), reduced DCP (P < 0.001) and increased blood velocity (33.65 ± 1.07 cm/s vs. 43.36 ± 1.25 cm/s, P < 0.001) at SFT stages, with increased blood-flow (P < 0.001). Both drugs increased downstream ESS. Esmolol significantly reversed abnormally increased ESS (P < 0.001) and increased upstream ESS compared with nicardipine (P < 0.001)., Conclusion: Beyond a similar reduction of AP, patients with UA and MCS could benefit more from the reduction of heart rate induced by esmolol (ChiCTR-TRC-10000964)., (© 2011 Blackwell Publishing Ltd.)

Background: Tacrolimus is commonly prescribed for immunosuppression, yet it can cause acute and chronic kidney injury. Continuous intravenous nicardipine (CIVN), prescribed for posttransplant hypertension, inhibits tacrolimus metabolism by cytochrome P450 (CYP) 3A4 and could lead to tacrolimus overexposure in patients genetically lacking the alternative pathway for tacrolimus metabolism, CYP3A5., Methods: We compared maximum 12-hr tacrolimus trough levels (MaxC0) and dose-adjusted MaxC0 in 12 cases treated with CIVN immediately after kidney transplantation with 26 controls (no CIVN). CYP3A5 genotype was determined for all cases., Results: Eight cases not expressing CYP3A5 (CYP3A5*3/*3) had higher median MaxC0 (24.3 ng/mL) than four cases expressing CYP3A5 (CYP3A5*1/*1; 13.9 ng/mL, P=0.028) and controls (14.6 ng/mL, P=0.003). Compared with the other two groups combined, CYP3A5*3/*3 cases had higher median dose-adjusted MaxC0 (330 vs. 175, P=0.012), less time to MaxC0 (42 vs. 72 hr, P<0.001), and more scheduled tacrolimus doses held per patient (1.75 vs. 0.4, P=0.007). Six of eight (75%) CYP3A5*3/*3 cases had potentially toxic MaxC0 (>20 ng/mL) compared with none of four CYP3A5*1/*1 cases and 3 of 26 (11.5%) controls (P<0.001, CYP3A5*3/*3 cases vs. all others)., Conclusion: CYP3A5 nonexpressors simultaneously treated with tacrolimus and CIVN may be at increased risk for tacrolimus toxicity.

Background: Laryngoscopy and tracheal intubation (LTI) after induction of general anesthesia often cause hypertension and tachycardia. Labetalol and nicardipine have been used to prevent and treat acute cardiovascular responses to LTI., Objective: The goal of this study was to compare the preventive and therapeutic effects of labetalol 0.4 mg/kg IV and nicardipine 20 μg/kg IV on hypertensive responses to LTI during induction of general anesthesia., Methods: Patients undergoing general anesthesia were randomly allocated to 4 groups. In part I (prevention), 80 patients were randomized to receive either 0.4 mg/kg of labetalol (n = 40) or 20 μg/kg of nicardipine (n = 40) 4 minutes before LTI. In part II (treatment), patients were randomized to receive 0.4 mg/kg of labetalol (n = 40) or 20 μg/kg of nicardipine (n = 40) after LTI if hypertension occurred. The number of additional study drug doses required by patients with hypertension (parts I and II) and time to return to normotension (part II) were recorded. Mean arterial pressure and heart rate were monitored, and rate-pressure product was calculated. Adverse events were also monitored., Results: A total of 130 patients (72 patients in part I and 58 patients in part II) were included in the analysis. In parts I and II, the number of patients who required additional doses of the study drug because of persistent hypertension was lower in the nicardipine groups than in the labetalol groups (P < 0.05). Mean arterial pressure was lower and heart rate was significantly higher over time in the nicardipine groups compared with the labetalol groups (P < 0.05) in parts I and II. In part II, time to return to normotension was shorter in the nicardipine treatment group than in the labetalol treatment group (61 [21] vs 130 [46] seconds; P = 0.01). No statistical differences were observed in the incidence of adverse events except for tachycardia in part I (2 cases in the labetalol prevention group vs 18 cases in the nicardipine prevention group; P = 0.01)., Conclusions: Patients who received nicardipine were less likely to require additional doses for either the prevention or treatment of hypertensive responses to LTI and responded to the study drug more rapidly than patients who received labetalol for the treatment of hypertensive responses to LTI. However, labetalol was associated with a lower incidence of tachycardia and less of an increase in rate-pressure product when used for the prevention of hypertension during LTI., (Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.)

It has been hypothesized that vasospasm is the prime mechanism of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Recently, it was found that clusters of spreading depolarizations (SDs) are associated with DCI. Surgical placement of nicardipine prolonged-release implants (NPRIs) was shown to strongly attenuate vasospasm. In the present study, we tested whether SDs and DCI are abolished when vasospasm is reduced or abolished by NPRIs. After aneurysm clipping, 10 NPRIs were placed next to the proximal intracranial vessels. The SDs were recorded using a subdural electrode strip. Proximal vasospasm was assessed by digital subtraction angiography (DSA). 534 SDs were recorded in 10 of 13 patients (77%). Digital subtraction angiography revealed no vasospasm in 8 of 13 patients (62%) and only mild or moderate vasospasm in the remaining. Five patients developed DCI associated with clusters of SD despite the absence of angiographic vasospasm in three of those patients. The number of SDs correlated significantly with the development of DCI. This may explain why reduction of angiographic vasospasm alone has not been sufficient to improve outcome in some clinical studies.

There are longstanding inconsistencies in the evidence thought to link vasospasm in the major branches of the Circle of Willis with delayed cerebral ischemia and poor outcome from aneurysmal subarachnoid hemorrhage (aSAH). The demonstrations, first in the laboratory, and more recently in patients with aSAH, of cortical spreading ischemia based on an abnormal response of the cerebral microcirculation to spreading depolarization offer an additional possible mechanism for delayed ischemia. That such events can occur in the substantial absence of proximal vasospasm is compatible with this concept, but the preliminary evidence needs support from more extensive studies.

Acute vasoreactivity testing for patients with pulmonary arterial hypertension (PAH) has been reported to be useful to identify patients with sustained beneficial response to oral calcium-channel blockers (CCBs), but there is a risk of exacerbation during the testing with oral CCBs. Therefore, we developed a testing method utilizing intravenous nicardipine, a short-acting CCB, and examined the safety and usefulness of acute vasoreactivity testing with nicardipine in PAH patients. Acute vasoreactivity testing with nicardipine was performed in 65 PAH patients. Nicardipine was administered by short-time continuous infusion (1 μg·kg⁻¹·min⁻¹ for 5 min and 2 μg·kg⁻¹·min⁻¹ for 5 min) followed by bolus injection (5 μg/kg). Hemodynamic responses were continuously measured using a right heart catheter. Acute responders were defined as patients who showed a decrease in mean pulmonary artery pressure of at least 10 mmHg to an absolute level below 40 mmHg with preserved or increased cardiac output. Two acute responders and sixty-three non-acute responders were identified. There was no hemodynamic instability requiring additional inotropic agents or death during the testing. Acute responders had good responses to long-term oral CCBs. The acute vasoreactivity testing with nicardipine might be safe and useful for identifying CCB responders in PAH patients.

Intracerebral hemorrhage (ICH) is a common stroke subtype in Japan. Hypertension is the leading cause. Perindopril Protection Against Recurrent Stroke Study (PROGRESS) revealed that blood pressure (BP) lowering could reduce stroke recurrence by 28% (ICH recurrence by 49%). The guideline for the management of hypertension (JSH2009) recommends BP control of ≤ 140/90 mm Hg for patients with prior stroke. BP is frequently elevated in acute ICH, although BP management strategy is controversial. The guideline from the American Stroke Association suggests if systolic BP (SBP) >180 mm Hg and there is no evidence of elevated intracranial pressure, then consider a modest reduction of BP. A nationwide survey revealed that SBP lowering to ≤ 160 mm Hg using intravenous nicardipine in acute ICH is a major strategy in Japan, and the safety was confirmed by a multicenter, prospective, observational study. Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT) and Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) showed the feasibility and safety of early rapid BP lowering to 140 mm Hg. INTERACT2 and ATACH II are the randomized trials to compare the guideline-based control (<180 mm Hg) and strict control (<140 mm Hg). We have just started to enroll patients to ATACH II from Japan on February 2012.

Objective: Intracisternal nicardipine prolonged release implants (NPRI) have been shown to be effective in the prophylaxis of cerebral vasospasm (VS). However, they cannot be used in patients following coil occlusion of the aneurysm. As a certain dissemination of nicardipine within the cerebrospinal fluid (CSF) has been described, we examined the feasibility of intraventricular use of NPRI in patients that underwent clip and coil occlusion of their aneurysms following aneurysmal subarachnoid haemorrhage (aSAH). By comparison with an historical control group, an estimation of their effectivity in regard to angiographic vasospasm and the development of cerebral infarction has been performed., Methods: Thirty-one patients suffering from aSAH were prospectively included in this trial. Study participants received prior to clipping (n = 17) or coiling (n = 14) 6 (n = 15) or 10 NPRI (n = 16) into the lateral ventricles. Physiological data were collected, proximal and global VS were determined using pre-operative and day 8 ± 1 angiography, and incidence of hydrocephalus and VS related infarcts were evaluated and compared to a historical control group consisting of 16 operated patients without NPRI implantation., Results: Intraventricular NPRI were tolerated well. There were no adverse side effects detectable, physiological variables such as heart rate (HR), mean arterial blood pressure (MAP), intracranial pressure (ICP) and electrolytes showed no difference compared to control. There was no difference in the proportion of patients that required CSF shunting. A significant positive angiographic effect could only be observed in clipped patients (proximal vessel diameters: control, 80 ± 30%; NPRI 90 ± 24%; incidence of moderate/severe global VS: control, 73%; NPRI, 41%)., Conclusions: The use of intraventricular NPRI seems to be safe and tolerated well. There is preliminary evidence for effectivity on angiographic VS for clipped patients only. A further increase of the effective dose might also exert efficacy in the subset of patients following coil occlusion.

Purpose of Review: Systemic hypertension (HTN) is a common medical condition affecting over 1 billion people worldwide. One to two percent of patients with HTN develop acute elevations of blood pressure (hypertensive crises) that require medical treatment. However, only patients with true hypertensive emergencies require the immediate and controlled reduction of blood pressure with an intravenous antihypertensive agent., Recent Findings: Although the mortality from hypertensive emergencies has decreased, the prevalence and demographics of this disorder have not changed over the last 4 decades. Clinical experience and reported data suggest that patients with hypertensive urgencies are frequently inappropriately treated with intravenous antihypertensive agents, whereas patients with true hypertensive emergencies are overtreated with significant complications., Summary: Despite published guidelines, most patients with hypertensive crises are poorly managed with potentially severe outcomes.

Hypertensive crises are divided into hypertensive urgencies and emergencies. Together they form a heterogeneous group of acute hypertensive disorders depending on the presence or type of target organs involved. Despite better treatment options for hypertension, hypertensive crisis and its associated complications remain relatively common. In the Netherlands the number of patients starting renal replacement therapy because of 'malignant hypertension' has increased in the past two decades. In 2003, the first Dutch guideline on hypertensive crisis was released to allow a standardised evidence-based approach for patients presenting with a hypertensive crisis. In this paper we give an overview of the current management of hypertensive crisis and discuss several important changes incorporated in the 2010 revision. These changes include a modification in terminology replacing 'malignant hypertension' with 'hypertensive crisis with retinopathy and reclassification of hypertensive crisis with retinopathy under hypertensive emergencies instead of urgencies. With regard to the treatment of hypertensive emergencies, nicardipine instead of nitroprusside or labetalol is favoured for the management of perioperative hypertension, whereas labetalol has become the drug of choice for the treatment of hypertension associated with pre-eclampsia. For the treatment of hypertensive urgencies, oral administration of nifedipine retard instead of captopril is recommended as first-line therapy. In addition, a section on the management of hypertensive emergencies according to the type of target organ involved has been added. Efforts to increase the awareness and treatment of hypertension in the population at large may lower the incidence of hypertensive crisis and its complications.

No-reflow is a failure to restore normal coronary flow despite appropriate treatment of coronary obstruction. It is most commonly seen during interventions in saphenous vein grafts and is associated with poor outcome. The cause of no-reflow is complex and multifactorial. Various mechanisms including vasospasm and distal embolization of debris released during the intervention have been explained as the cause of no-reflow. Treatment to prevent or reverse no-reflow includes, but is not limited to, protective devices and intracoronary vasodilators. Intracoronary nicardipine seems to be the best option in preventing no-reflow regarding its minimal systemic side effects, modest negative inotropic and chronotropic effects, duration of action and feasibility of use. The goal of this manuscript is to review the effects of prophylactic intragraft nicardipine injection for prevention of no-reflow during saphenous vein graft intervention.

Introduction: the aim of this study was to evaluate the management of HELLP syndrome at Josephine-Bongo Maternity Hospital., Study Population and Methods: the retrospective study included all women admitted to the intensive care unit of our hospital from 1 January 2004 through 30 December 2007 with HELLP syndrome. The characteristics studied included: age, parity, number of previous pregnancies, antenatal monitoring, term at onset, clinical and laboratory signs, treatment, complications, perinatal and neonatal mortality and duration of intensive care unit admission., Results: nine patients, mainly primiparas with an average age of 29.7 ± 6.5 years were admitted to intensive care. HELLP syndrome was diagnosed at a mean term of 33 ± 2.7 weeks. The clinical signs noted included the following: jaundice (100%), headaches (100%) and epigastric pain (67%). The laboratory analysis showed: a mean haemoglobin level of 8.7 ± 1.2 g/dL, an average platelet level of 70,900 ± 27,052.9/mm(3), and mean transaminase levels of 120 ± 60 UI/L for aspartate aminotransferase (AST) and 99 ± 41.1 UI/L for alanine aminotransferase (ALT). Hypertension was treated by continuous intravenous administration of nicardipine. The fetal pulmonary development was ensured with betamethasone. Delivery was by caesarean for four women (44%) and vaginal for the other five (56%). One maternal death was noted, related to a rupture of a subcapsular haematoma of liver., Conclusion: in view of the extent of perinatal morbidity and mortality associated with HELLP syndrome, abdominal ultrasonography to detect any subcapsular haematoma of liver should be performed to determine the need for immediate delivery. It would be appropriate to provide the Josephine-Bongo Maternity Hospital with a neonatal intensive care unit of high quality.

Posterior reversible encephalopathy syndrome (PRES) is a reversible, predominantly posterior, leukoencephalopathy associated with renal insufficiency, hypertension, or immunosuppressant drugs. We describe two children with PRES whose primary diagnoses were idiopathic nephrotic syndrome and lupus nephritis. Cranial magnetic resonance (MR) imaging at the onset of PRES showed strong hyperintense signals on diffusion-weighted imaging with restricted apparent diffusion coefficient values predominantly in the posterior region. Such findings have been rarely reported in children with PRES and initially suggested irreversible brain damage; however, both children fully recovered clinically as well as radiologically. Our findings suggest the limitations of cranial MR imaging for diagnosing PRES. Further experience with cranial MR imaging, including diffusion-weighted imaging with apparent diffusion coefficient mapping, is required to improve diagnostic accuracy and the ability to predict outcomes in patients with early-stage PRES. At present, initial imaging studies do not necessarily provide sufficient evidence for a firm diagnosis of PRES or the prediction of outcomes.

Purpose: A case of severe macroglossia and angioedema in a child with Burkitt lymphoma who was treated with two dihydropyridine calcium-channel blockers is reported., Summary: An eight-year-old white boy arrived at the pediatric emergency department with complaints of abdominal pain and distention after an episode of mild abdominal trauma. Physical examination results were significant for diffuse abdominal tenderness and distention, with a large palpable mass in the right quadrants. Computed tomography revealed a large abdominal mass, and a biopsy confirmed a diagnosis of Burkitt lymphoma. Before initiation of chemotherapy, the child developed tumor lysis syndrome, with subsequent renal failure and cardiorespiratory compromise. Once the patient was stabilized and sedated on mechanical ventilation, tumor-directed chemotherapy was initiated, and rapid tumor regression ensued. To control episodes of hypertension, nicardipine was initiated and titrated to achieve the blood pressure goals. Three days after initiation of nicardipine therapy, the child developed facial swelling and significant, protruding macroglossia. Eight days after nicardipine initiation, a tracheotomy was required due to upper airway obstruction; at that time, the patient was converted to amlodipine administered via nasogastric tube for continued blood pressure control. The boy's macroglossia persisted for another 18 days, until a multi-disciplinary drug therapy review resulted in the discontinuation of amlodipine. Within one week of the withdrawal of amlodipine, the child's macroglossia was completely resolved., Conclusion: An eight-year-old boy with Burkitt lymphoma developed severe macroglossia and angioedema when treated with nicardipine. The reaction persisted throughout treatment with amlodipine and resolved quickly after amlodipine was withdrawn.

TAC is commonly prescribed in KTX recipients, though overexposure can be nephrotoxic. CIVN, used to treat post-KTX hypertension, may inhibit TAC metabolism resulting in overexposure and potential toxicity. We present two case reports and analysis of 2068 KTXs from the PHIS to characterize post-KTX intravenous anti-hypertensive use and to determine whether CIVN in TAC-treated patients would predict "immunosuppressive drug causing adverse effects in therapeutic use" (E-code E9331). CIVN was ordered in 11% of KTXs and prescribing increased from 6.2% in 2003 to 10.3% in 2008 (p=0.003, Mantel-Haenszel chi-square test). AEI were reported in 7.1% of TAC-treated patients with CIVN orders compared to 3% of those without (p=0.003, chi-square test). In univariate analysis using GEEs, AEI were twofold more likely in patients with CIVN orders than patients without (AOR 2.1, 95% CI 1.03-4.17) and threefold more likely than patients with orders for other continuous intravenous anti-hypertensives (AOR 3.2, 95% CI 1.09-9.08). In multivariate analysis, only CIVN significantly predicted AEI (AOR 2.8, 95% CI 1.29-6.04). Thus, until clinical studies to fully characterize this interaction are completed, CIVN should be used with caution in TAC-treated individuals., (© 2010 John Wiley & Sons A/S.)

Objective: To determine the efficacy and safety of labetalol for hypertensive crisis in children ≤ 24 months of age., Design: Retrospective chart review. Statistical analysis utilized analysis of variance for continuous data, chi-square tests for nominal data, and linear regression., Setting: A 737-bed pediatric teaching institution., Patients: Twenty-seven patients ≤ 24 months of age were treated with 37 intravenous infusions of labetalol, nicardipine, or nitroprusside for hypertensive crisis or hypertensive urgency., Interventions: None., Measurements and Main Results: The primary end point consisted of time to 20% reduction in systolic blood pressure. Primary safety end points measured the prevalence of deleterious effects of labetalol. Continuous infusion of labetalol reduced mean systolic blood pressure by at least 20% in < 8 hrs. This effect was similar to nicardipine and nitroprusside infusions. The reported side effects were similar in each group. Patients receiving labetalol and presenting with ischemic or traumatic brain injury were likely to develop hypotension requiring infusion discontinuation., Conclusions: Continuous intravenous labetalol infusion is efficacious for treatment of hypertensive crisis in children ≤ 24 months of age. Aside from patients presenting with ischemic or traumatic brain injury, labetalol was safe to use in this population for hypertensive emergencies and had a satisfactory adverse effect profile. Labetalol may reach dose saturation at a much lower dose in young children in comparison to adults. Clinicians should use caution when initiating labetalol infusions in young patients with brain injury.

Regardless of numerous efforts there is no prophylactic treatment proven to be effective in the prevention of cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH). As systemic administration of vasoactive drugs has been associated with significant side effects and insufficient efficacy, intrathecal administration of nicardipine prolonged-release implants (NPRI) has been developed. At the time of surgical clipping of the ruptured aneurysm, NPRIs are positioned next to the large cerebral arteries. Several clinical protocols revealed that NPRIs dramatically reduce the incidence and severity of angiographic vasospasm, which was paralled by a reduction in cerebral infarction and delayed ischemic neurologic deficit. On average, the incidence of angiographic vasospasm decreased from approximately 70% to less than 10%. Efficacy seemed to be dose-dependent and reduced for peripheral vasospasm. Nevertheless, a significant improvement of functional outcome was demonstrated. A separate patient series demonstrated the efficacy of fewer NPRIs in the perichiasmatic cistern. Further investigations were performed in comparison to coiled patients and with intraventricular implantation of NPRIs, which had a less pronounced effect. Overall, NPRIs are a most promising option for the prevention of cerebral vasospasm after SAH and large controlled trials are needed to further confirm these results.

Unlabelled: BRIEF SUMMARY: We describe the use of adenosine-induced cardiac arrest to facilitate intracranial aneurysm clip ligation., Background: Cerebral aneurysms are highly variable which may result in difficult surgical exposure for clip ligation in select cases. Secure clip placement is often not feasible without temporarily decompressing the aneurysm. This can be accomplished with temporary clip ligation of proximal vessels, or with deep hypothermic circulatory arrest on cardiopulmonary bypass, although these methods have their own inherent risks. Here we describe an alternate method of decompressing the aneurysm via adenosine-induced transient asystole., Methods: We examined the records of 27 patients who underwent craniotomy for cerebral aneurysm clipping in which adenosine was used to induce transient asystole to facilitate clip ligation. Duration of adenosine-induced bradycardia (heart rate <40) and hypotension (SBP < 60) recorded on the electronic anesthesia record and outcome data including incidence of successful clipping, intraoperative and postoperative complications, and mortality were recorded., Results: Satisfactory aneurysm decompression was achieved in all cases, and all aneurysms were clipped successfully. The median dose of intravenous adenosine resulting in bradycardia greater than 30 seconds was 30 mg. The median dose of adenosine resulting in hypotension greater than 30 seconds was 15 mg, and greater than 60 seconds was 30 mg. One case of prolonged hypotension after rapid redosing of adenosine required brief closed chest compressions before circulation was spontaneously restored. No other adverse events were observed., Conclusions: Adenosine cardiac arrest is a relatively novel method for decompression of intracranial aneurysms to facilitate clip application. With appropriate safety precautions, it is a reasonable alternative method when temporary clipping of proximal vessels is not desirable or not possible.

Introduction: Our purpose was to compare the safety and efficacy of food and drug administration (FDA) recommended dosing of IV nicardipine versus IV labetalol for the management of acute hypertension., Methods: Multicenter randomized clinical trial. Eligible patients had 2 systolic blood pressure (SBP) measures ≥180 mmHg and no contraindications to nicardipine or labetalol. Before randomization, the physician specified a target SBP ± 20 mmHg (the target range: TR). The primary endpoint was the percent of subjects meeting TR during the initial 30 minutes of treatment., Results: Of 226 randomized patients, 110 received nicardipine and 116 labetalol. End organ damage preceded treatment in 143 (63.3%); 71 nicardipine and 72 labetalol patients. Median initial SBP was 212.5 (IQR 197, 230) and 212 mmHg (IQR 200,225) for nicardipine and labetalol patients (P = 0.68), respectively. Within 30 minutes, nicardipine patients more often reached TR than labetalol (91.7 vs. 82.5%, P = 0.039). Of 6 BP measures (taken every 5 minutes) during the study period, nicardipine patients had higher rates of five and six instances within TR than labetalol (47.3% vs. 32.8%, P = 0.026). Rescue medication need did not differ between nicardipine and labetalol (15.5 vs. 22.4%, P = 0.183). Labetalol patients had slower heart rates at all time points (P < 0.01). Multivariable modeling showed nicardipine patients were more likely in TR than labetalol patients at 30 minutes (OR 2.73, P = 0.028; C stat for model = 0.72), Conclusions: Patients treated with nicardipine are more likely to reach the physician-specified SBP target range within 30 minutes than those treated with labetalol.

Reversible posterior leukoencephalopathy syndrome (RPLS) is a recently identified clinical and radiologic entity. The characteristic radiologic findings are bilateral gray and white matter edema in the posterior regions of the cerebral hemispheres. The typical clinical syndrome includes headache, confusion, visual symptoms, and seizures. RPLS most often occurs in the setting of hypertensive crisis, preeclampsia, or with cytotoxic immunosuppressive therapy, but many other clinical settings are described, such as cryoglobulinemia, hemolytic uremic syndrome, systemic lupus erythematosus, and use of erythropoietin. A 24-year-old man, diagnosed as having anaphylactoid purpura nephritis at 12 years of age and who started peritoneal dialysis (PD) at 23 years of age, was admitted to our hospital with a seizure and consciousness disturbance. His blood pressure (BP) and body fluid volume had not been controlled well because of poor compliance with medication and PD. T2-weighted magnetic resonance imaging (MRI) revealed high signal intensity changes restricted to the cortex and subcortical white matter of the cerebellum. On the other hand, diffusion-weighted imaging showed an isointense signal. From these findings, he was diagnosed as having RPLS. With appropriate control of BP and volume control by PD and hemodialysis, his symptoms improved, and a follow-up cranial MRI 1 month later was almost normal. To the best of our knowledge, this is the first report of RPLS in an adult PD patient.

Cardiovascular diseases are a leading cause of hospitalizations and death in the United States and elsewhere in the world. Developing new therapeutic agents for cardiovascular diseases has always been the priority for the pharmaceutical industry because of the huge potential market for these drugs. Some of these newer drugs are frequently used in the practice of cardiovascular anesthesiology. This article reviews the recent advances in cardiovascular medications related to the practice of cardiac anesthesia., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Introduction: Various conservative treatments for Peyronie's disease (PD) have been attempted over the years. Intralesional verapamil injection has been tested in prospective randomized studies, but the effect of this treatment seems insufficient. Nicardipine is a calcium antagonist alternative to verapamil and is reportedly more effective in vitro., Aim: The objective of our study was to evaluate the usefulness of intralesional nicardipine injection as a conservative treatment for PD in the transition period of acute and chronic phase., Methods: Eighty-six patients (age: 38-72 years, mean: 52) were enrolled in this study. A total of 74 patients were assigned randomly to nicardipine group (10 mg diluted in 10 mL of distilled water daily, N=37) and control group (10 mL of saline water, N=37). A total of six injections were administrated biweekly., Mean Outcome Measure: The subjects were assessed by International Index of Erectile Function (IIEF)-5 and international pain scale. The plaque size was measured by ultrasonography after 20 µg intracavernosal injection of alprostadil (prostaglandin E1). The penile curvature was also measured by taking a photograph at maximum rigidity., Results: A reduction of pain score was seen throughout the course of treatment in both groups with a significant difference between the nicardipine and control groups (multiple analysis of variance test, P=0.019). A significant improvement of IIEF-5 score occurred only in the nicardipine group at 48 weeks after the initiation of treatment (P<0.01). The plaque size was significantly reduced at 48 weeks only in the nicardipine group (12 points, P=0.0004 by paired t-test). The penile curvature was significantly improved in both groups (P<0.01) without significant difference between them (P=0.14). There were no severe side effects, such as hypotension or other cardiovascular events., Conclusion: Our findings indicate that intralesional nicardipine injection is clinically effective as a conservative treatment for PD in the transition period of acute and chronic phase., (© 2010 International Society for Sexual Medicine.)

Background: No-reflow (NR) phenomenon is a well-known problem, often accompanying percutaneous coronary intervention for acute ST elevation myocardial infarction (STEMI). There are little data on effects of pharmacologic therapy on the resolution, outcome, and long-term natural history of NR., Objective: Retrospectively assess incidence, management, and prognosis of NR in a tertiary referral hospital., Methods: Study included patients with STEMI, treated with percutaneous coronary intervention (PCI). Effect of pharmacologic therapy and long-term outcome were assessed. NR was defined by thrombolysis in myocardial infarction (TIMI) < 3 or myocardial blush grade (MBG) < 3., Results: Of 347 identified subjects, NR occurred in 110 (32%) by TIMI and 198 (57%) by MBG. Higher incidence was identified in men versus women (34% vs. 25% by TIMI, P = 0.08; and 60% vs. 48% by MBG, P = 0.04). Pharmacologic therapy was equally effective in restoring normal flow, increasing TIMI score from 1.62 ± 0.07 to 2.78 ± 0.06 (P < 0.0001) and MBG score from 0.43 ± 0.08 to 2.09 ± 0.11 (P < 0.0001). Twenty-three percent who did not receive pharmacologic therapy developed clinical composite of congestive heart failure, cardiogenic shock, and/or death; only 9% of patients who received pharmacologic therapy developed this composite. Patients with severe NR despite treatment had poorer prognosis. Sixty-five percent of patients who survived and had repeat angiogram about 1.5 years later had spontaneous improvement in coronary flow by MBG., Conclusion: NR is common in STEMI. Treatment with nicardipine, nitroprusside, and verapamil are equally effective in improving flow. If not treated, prognosis is poor., (©2010, Wiley Periodicals, Inc.)

Introduction: To evaluate the efficacy, tolerability, and safety of nicardipine infusion in controlling the elevated blood pressure after subarachnoid hemorrhage (SAH)., Methods: Nicardipine infusion was initiated if the individual pre-specified systolic blood pressure (SBP) level goal, mandated by the admitting neurosurgeon, was not met. Systolic and diastolic BPs were measured on admission, hourly during the infusion and 12 h before and after the infusion., Results: Twenty-eight patients with SAH required 50 nicardipine infusions in order to achieve a mean SBP goal of 152 mmHg. The 3,112 extracted BP measurements showed that mean infusion SBP was significantly lower than admission and pre-infusion SBP (mean 146.5 vs. 177.1 and 155.6 mmHg, P < 0.001, respectively) and significantly higher than post-infusion SBP (146.5 vs. 142.6 mmHg, P = 0.002). Five infusions were stopped prematurely, because of hypotension (n = 3), emergent surgery (n = 1), and failure to reach the SBP goal (n = 1). Rebleeding was not observed in any patient. Nicardipine achieved SBP control in 59.9% of hourly infusion measurements, with a trend for higher proportion of success with higher SBP goals., Conclusion: In this study, nicardipine infusion was a safe and moderately effective treatment for BP control in patients with SAH. Although SBP during nicardipine infusion was higher than the pre-specified goal in a significant percentage of hourly observations, this may be due to the drug administration protocol and other factors such as analgesia and sedation.

Objective: For the first line tocolysis, calcium channel blockers (CCB)--oral nifedipine (Adalate®) or intravenous nicardipine (Loxen®)--are frequently used in France. No study compared nifedipine and nicardipine in management of threatened preterm delivery. From data of a French observational study, we compared factors associated with the use of nifedipine and nicardipine. Efficacy and tolerance of the two treatments were also compared., Methods: It was a secondary analysis of EVAPRIMA study, a practice survey describing management of threatened preterm delivery in 107 French maternity units. Only women who received calcium channel blockers in their first line tocolytic therapy were included. We studied obstetrical factors associated with the choice of nifedipine or nicardipine. We also analyzed factors associated with a delivery within seven days following admission using univariate and multivariate analysis. Adverse secondary effects were compared between women who received nifedipine or nicardipine., Results: Three hundred and four women received calcium channel blockers for their first line tocolytic therapy, in 73 maternity units: 93 (30.6%) women received oral nifedipine and 211 (69.4%) intravenous nicardipine. The same CCB was always prescribed in 69 maternity units. Admission after in utero transfer was less frequent among women who received nifedipine (6.5% versus 17.1%, P=0.01). Premature rupture of the membranes was also less frequent among women who received nifedipine (4.3% versus 13.7%, P=0.02), in comparison with women who received nicardipine. Median duration between admission for threatened preterm labor and delivery was longer when nifedipine was used (44 days versus 36 days, P=0.04). After adjustment on obstetrical factors, the risk to have a delivery within 7 days following admission was not significantly different between nifedipine and nicardipine groups (adjusted OR=0.5 [0.2-1.2]). Among women who received nifedipine only two cases (2.1%) of adverse event were reported with only one case needing a switch of treatment. Thirteen (6.2%) cases of adverse event were reported among women who received nicardipine (P=0.16); in three cases it motivated a switch. However, due to bias and limits inherent in such studies, our results should be interpreted cautiously., Conclusion: Nicardipine is the first choice for French obstetricians in management of severe threatened preterm delivery. However, intravenous nicardipine does not increase gestational duration in comparison with oral nifedipine., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Background: The aim of this study was to compare the frequency of hypotension induced by oxytocin antagonist atosiban and nicardipine., Methods: This case-control study enrolled 14 pregnant women presenting with threatening premature delivery treated with atosiban and managed by a physician-staffed Emergency Medical Service Department (French Emergency Medical Service system) during inter-hospital transfers. A control group of 42 consecutive pregnant women presenting with threatening premature delivery managed during inter-hospital transfers during the same period and treated with nicardipine was set up. The control group was recruited after matching on confounding variables: age 38 years or less and no previous cardiovascular disease to avoid factors related to the occurrence of cardiovascular events, duration of out-of-hospital management of at least 60 min to have similar likelihood of side-effect occurrence, and parity 2 or less and gestational age from 25 to 32 weeks to make comparable groups from the obstetrical viewpoint. Frequency of hypotension was compared between the two groups., Results: Hypotension was observed in two patients (8%) in the atosiban-group and in five patients (14%) in the nicardipine-group, which is not significantly different (P>0.99)., Conclusion: Despite the notion that oxytocin antagonist atosiban has limited or no systemic adverse effects, these results suggest that this cost-consuming drug does not avoid hypotension and cannot help to reduce the level of monitoring.

Background: Cerebral arterial vasospasm and delayed ischemic neurological deficits are significant contributors to morbidity and mortality following aneurysmal subarachnoid hemorrhage. Additional treatment modalities are needed. Intraventricular nicardipine has been suggested as a potential therapy for the treatment of cerebral vasospasm. It is an appealing option for multiple reasons: many of these patients already have ventricular drains in place, it can be safely administered at the bedside, and can be used in patients for whom conventional therapies are either not effective or not tolerated., Methods: Retrospective case series of all patients who received intraventricular nicardipine for the treatment of cerebral vasospasm from January 2006 to June 2007 at a university tertiary care hospital., Results: Sixty-four patients received intraventricular nicardipine during the study period. Forty-two patients met inclusion criteria. Intraventricular nicardipine administration was associated with a reduction of the mean cerebral blood flow velocity of 26.3 cm/s in the middle cerebral artery and 7.4 cm/s in the anterior cerebral artery. This reduction was maintained over 24 h with continued administration., Conclusions: Intraventricular nicardipine was associated with a significant and sustained reduction in mean cerebral blood flow velocity as measured by transcranial Doppler when used in the treatment of suspected cerebral vasospasm following aneurysmal subarachnoid hemorrhage. We do not find significant safety concerns related to elevations of intracranial pressure or ventricular catheter related infections. Further prospective studies are warranted to better determine the efficacy and safety of this therapy.

Purpose of Review: In a rapidly advancing specialty, it is essential to review the recent studies of alternative new treatments and present their efficacy, safety and outcome. We discuss the recent advances in the endovascular treatment of cerebral vasospasm following aneurysmal subarachnoid hemorrhage in the past few years with special focus on the literature regarding this subject in the last 18-24 months., Recent Findings: The recent findings are as follows: effect of papaverine on brain oxygen; recent evaluation concerning nimodipine use; combined intraarterial and intravenous use of milrinone; illustration of the numerous recent studies on nicardipine; the safety and efficacy of high-dose intraarterial verapamil; outcome and adverse effects of intraarterial fasudil; transluminal balloon angioplasty; and recent evaluation of its efficacy and evaluation of its prophylactic use., Summary: Endovascular treatment, including intraarterial vasodilators and transluminal balloon angioplasty, has a very important place in the management of symptomatic vasospasm related to aneurysmal subarachnoid hemorrhage. The efficacy of intraarterial vasodilators has been proven. Numerous studies and analysis of different treatments of cerebrovascular vasospasm took place in the past period. This allowed more understanding and evaluation of their outcome, safety and efficacy helping physicians to choose better treatments to adopt. It emphasizes also the aspects that need more study and research.

The management of the PE patient requires admission in order to perform a meticulous assessment of the mothers' and fetal state, distinguishing between the severe and the mild forms. In moderate forms, the pregnancy is allowed to reach the 37(th) week of gestation. In severe forms of PE, the pregnancy is only allowed to continue under stringent monitoring. Before the 34(th) week of amenorrhea is reached, corticosteroid therapy and transfer to an adapted maternity are recommended. The true benefit provided by antihypertensive therapy in the moderate forms of PE is very limited. The presently recommended antihypertensive agent is nicardipine, which can be used in association with magnesium sulphate provided there is appropriate monitoring., (Copyright 2010 Elsevier Masson SAS. All rights reserved.)

Objective: To determine the feasibility and acute (i.e., within 72 hrs) safety of three levels of systolic blood pressure reduction in subjects with supratentorial intracerebral hemorrhage treated within 6 hrs after symptom onset., Design: A traditional phase I, dose-escalation, multicenter prospective study., Settings: Emergency departments and intensive care units., Patients: Patients with intracerebral hemorrhage with elevated systolic blood pressure > or = 170 mm Hg who present to the emergency department within 6 hrs of symptom onset., Intervention: Intravenous nicardipine to reduce systolic blood pressure to a target of: (1) 170 to 200 mm Hg in the first cohort of patients; (2) 140 to 170 mm Hg in the second cohort; and (3) 110 to 140 mm Hg in the third cohort., Measurements and Main Results: Primary outcomes of interest were: (1) treatment feasibility (achieving and maintaining the systolic blood pressure goals for 18-24 hrs); (2) neurologic deterioration within 24 hrs; and (3) serious adverse events within 72 hrs. Safety stopping rules based on neurologic deterioration and serious adverse events were prespecified and approved by an NIH-appointed Data and Safety Monitoring Board, which provided oversight on subject safety. Each subject was followed-up for 3 months to preliminarily assess mortality and the clinical outcomes. A total of 18, 20, and 22 patients were enrolled in the respective three tiers of systolic blood pressure treatment goals. Overall, 9 of 60 patients had treatment failures (all in the last tier). A total of seven subjects with neurologic deterioration were observed: one (6%), two (10%), and four (18%) in tier one, two, and three, respectively. Serious adverse events were observed in one subject (5%) in tier two and in three subjects (14%) in tier three. However, the safety stopping rule was not activated in any of the tiers. Three (17%), two (10%), and five (23%) subjects in tiers one, two, and three, respectively, died within 3 months., Conclusions: The observed proportions of neurologic deterioration and serious adverse events were below the prespecified safety thresholds, and the 3-month mortality rate was lower than expected in all systolic blood pressure tiers. The results form the basis of a larger randomized trial addressing the efficacy of systolic blood pressure reduction in patients with intracerebral hemorrhage.

Background: Elevated blood pressure (BP) causes rebleeding or enlargement of intracerebral hematomas., Aims: How a long-acting oral calcium channel blocker, cilnidipine, could control BP in the acute stage of cerebral hemorrhage was evaluated., Methods and Results: Cilnidipine given within 3 days of hospitalization has more benefit than cilnidipine given after 4 days of hospitalization; it can reduce the amount of intravenous nicardipine, and it can help to maintain the BP below 80% of the initial BP. Surgical removal of the hematoma has no benefit in reducing the amount of intravenous nicardipine and maintaining the BP below 80% of the initial BP., Conclusion: In order to reduce the total amount of intravenous nicardipine and to maintain the BP below 80% of the initial BP, oral administration of a long-acting N-type calcium channel blocker, cilnidipine, is useful and important, independent of whether the hematomas are surgically removed.

Objective: The aim of this study is to explore if ABCG2 is related to the grade of glioma and resistance to chemotherapeutic drug for glioma., Methods: The ABCG2 expression and distribution among glioma tissues of different grades and other samples were examined using tissue microarray technique. The enhancement of sensitivity of CD133+ glioma stem cells to chemotherapeutic agent, mitoxantone through addition of ABCG2 competitive inhibitor nicardipine was testified by MTT assay and FACS analysis., Results: The positive immunostaining of ABCG2 was observed in less than 10% of low-grade gliomas (3/31 in grade I + II) and in more than 40% of high-grade gliomas (16/37 in grade III + IV), which was statistically different (chi (2) = 10.710, P = 0.0011). In samples consisting of glioma stem cells (CD133+), the positive-straining rate was 100% (4/4), while in CD133- fraction, no positive staining was observed. A simultaneous treatment of CD133+ tumor cells with concentration-dependent mitoxantone (10(-5)-1 microM) and 2.5/5.0 microM nicardipine resulted in synergistic cytotoxicity. The apoptotic rate of CD133+ cells treated with mitoxantone plus nicardipine was significantly higher than that treated with mitoxantone alone (58.54 +/- 7.06% vs. 30.7 +/- 3.79%, P < 0.01)., Conclusions: Our results showed that ABCG2 is also expressed in glioma stem cells and the expression level of ABCG2 is positively associated with the increasing pathological grade of glioma (poor cell differentiation). ABCG2 plays a key role in glioma cells resistance to mitoxantone, chemotherapeutic drug for glioma. Thus, inhibition of ABCG2 protein activity by nicardipine in glioma can sensitize it to mitoxantone, which may lead to better treatment strategies for cancers.

The authors describe the case of a 13-year-old boy who presented with an intraventricular hemorrhage caused by a left trigonal arteriovenous malformation. After an initial recovery, the patient experienced complete right-sided paresis on posthemorrhage Day 6. Severe cerebral vasospasm was found on MR angiography and confirmed on conventional cerebral angiography. Intraarterial nicardipine injection and balloon angioplasty were successfully performed with improved vasospasm and subsequent neurological recovery. Cerebral vasospasm should be considered in the differential diagnosis for neurological deterioration following an arteriovenous malformation hemorrhage, and aggressive treatment can be administered to prevent ischemia and further neurological deficits.

Nicardipine is a dihydropyridine-type Ca(2+) channel blocker (CCB) with strong antihypertensive activity and with a peculiar cerebrovascular profile. This paper has reviewed the main controlled clinical studies on nicardipine in pathologies associated with cerebrovascular impairment. Subarachnoid haemorrhage (SAH) is managed with CCBs to prevent vasospasm and improve clinical outcomes. Nimodipine is the CCB licensed for this indication. Former studies did not demonstrate an advantage of nicardipine versus nimodipine in SAH. A more recent approach administering the drug intra-arterially or using implants of nicardipine prolonged-release showed a decreased incidence of vasospasm, delayed ischemic deficits and improved clinical outcome after severe SAH. Nicardipine is recommended for elevated blood pressure after acute ischemic stroke or intracerebral haemorrhage and is effective in prevention of stroke. More recent investigations were focused on the treatment of cognitive deterioration of vascular origin. In this setting nicardipine has been investigated in more than 6000 patients, with improvement of cognitive deterioration in more than 60% of patients treated. The anti-hypertensive activity of nicardipine, its safety and effectiveness in cognitive domain, suggests re-considering this drug in the treatment of cognitive impairment of vascular origin and for reducing the risk of recurrent stroke in patients at high risk of it.

The no-reflow phenomenon is a poorly understood complication of percutaneous coronary intervention in which diminished blood flow to distal microvascular beds persists despite the successful treatment of the occlusive lesion from the epicardial coronary artery or arteries. In this contemporary review we endeavour to discuss the pathophysiology of coronary no-reflow, understand the predictors and describe current pharmacological and mechanical strategies to prevent and treat coronary no-reflow.

Objectives: To investigate the renoprotective effect of nicardipine in patients undergoing robot-assisted laparoscopic radical prostatectomy (RALRP) in a prospective trial. Superior visualization of the increasingly performed RALRP requires pneumoperitoneum and extreme head-down tilt, both of which are associated with a decrease in postoperative renal function. Nicardipine causes preferential dilation of the renal arterioles and attenuates renal dysfunction after cardiac surgery., Methods: After we obtained institutional review board approval, we randomly treated 100 patients undergoing RALRP with a continuous infusion of nicardipine at a rate of 0.5 microg/kg/min (nicardipine group, n = 50) or with normal saline (control group, n = 50) during surgery. We measured the serum creatinine (Cr) level and estimated glomerular filtration rate (eGFR) 1 day before surgery and the first and third postoperative days (POD 1 and 3, respectively)., Results: Patients' characteristics and operative data were similar between groups. The serum Cr was significantly higher and the eGFR was significantly lower in the control group at POD 1. The number of patients having renal insufficiency (eGFR < 60 mL/min/1.73 m(2)) and abnormal serum creatinine level (>1.4 mg/dL) was significantly greater in the control group (9 vs 1, and 4 vs none, respectively) at POD 1., Conclusions: Continuous infusion of low-dose nicardipine during RALRP seems to offset the deleterious effects of inevitable pneumoperitoneum and extreme head-down tilt on renal function in preserving the eGFR and attenuating the development of renal insufficiency in the immediate postoperative period.

Clevidipine is an arterial, selective, dihydropyridine calcium channel blocker with an ultrashort half-life. In this prospective, randomized, open-label, parallel-comparison trial series, the safety and efficacy of intravenous clevidipine with nitroglycerin, sodium nitroprusside and nicardipine in hypertensive patients during cardiac surgery were compared. No differences in the incidences of myocardial infarction, stroke or renal dysfunction were observed between treatment groups. Mortality was similar between the clevidipine-nitrogylcerine- and clevidipine-nicardipine-treated groups, whereas mortality appeared to be greater in the sodium nitroprusside group compared to clevidipine (p = 0.04 in a univariant analysis). Clevidipine was significantly more effective in blood pressure control compared with nitroglycerin (p = 0.0006) or sodium nitroprusside (p = 0.003) and was associated with fewer blood pressure excursions compared with nicardipine as a predetermined blood pressure range was narrowed.

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder with a mortality rate of up to 90% if left untreated, and is characterized by microvascular thrombi, mainly in small arteries and capillaries, thrombocytopenia, hemolysis, and neurological abnormalities. Malignant hypertension (HTN) is a clinical syndrome characterized by severe hypertension associated with end-organ damage; including encephalopathy, renal dysfunction, and retinal hemorrhage due to platelet aggregation in the microcirculation leading to thrombotic microangiopathy (TMA). These are similar to TTP. Malignant hypertension can cause endothelial injury and fibrinoid necrosis in the vessel wall which results in its clinical manifestations. Therefore, it is difficult to differentiate malignant hypertension from TTP. However, it is critical to differentiate these two entities, as early initiation of plasmapheresis in TTP can be life saving. TTP is considered a masquerader as it can present with few clinical features and, if the index of suspicion is not very high, lead to mortality.

Injectable nicardipine is increasingly being used to manage neurovascular conditions. To better understand its place in therapy, we conducted an evidenced-based literature review. Two-hundred twenty-three article abstracts were identified; after independent review by two individuals and a supplemental manual search, 29 were deemed relevant and were included in this review. Nicardipine has been studied or recommended for management of hypertension in many neurovascular settings (ischemic stroke, intracerebral hemorrhage, craniotomy, and spinal surgery), for vasospasm in aneurysmal subarachnoid hemorrhage, and in acute traumatic brain injury. In the management of hypertension in acute stroke, nicardipine is one of several recommended options available; expert opinion forms the basis of these recommendations in clinical guidelines, with limited randomized controlled trial evidence to support its use. Among the various antihypertensive agents, nicardipine has the highest drug acquisition cost. In two meta-analyses, intravenous nicardipine had no impact on patient outcomes (death, disability) in patients with acute traumatic brain injury (relative risk [RR] 0.25, 95% confidence interval [CI] 0.05-1.27) or in patients with aneursymal subarachnoid hemorrhage (RR 0.97, 95% CI 0.78-1.20). Intraarterial nicardipine reduced angiographic diameter (p value not reported) and peak systolic velocities on transcranial Doppler images (p<0.001) in published case series. Given nicardipine's high cost relative to that of other agents and the limited evidence to support its use in patients with neurovascular conditions, this drug should be considered only in patients who have failed or have contraindications to alternative agents in the management of hypertension. Although intraarterial nicardipine appears to be promising in aneurysmal subarachnoid hemorrhage, well-designed studies are needed in this setting before its use can be routinely recommended.

Purpose: Pharmacotherapeutic options for the treatment of preeclampsia are reviewed., Summary: Risk factors for the development of preeclampsia include microvascular diseases, such as diabetes mellitus; vascular and connective tissue disorders; hypertension; antiphospholipid antibody syndrome; and nephropathy. Several pathophysiological factors contribute to the development of the preeclamptic state, including vasospasm onset, coagulation system activation, increased inflammatory response, and ischemia. The specific agents used for the treatment of preeclampsia are dependent on a number of factors including symptom severity, maternal or fetal compromise, the progression to eclampsia, gestational period, and cervical status. The diagnosis of preeclampsia beyond the gestation period of 38 weeks requires delivery. The presence of maternal compromise or eclampsia at gestation greater than 20 weeks also necessitates delivery. In cases of chronic or mild hypertension, oral methyldopa may be administered on an outpatient basis. Intravenous hydralazine is a commonly administered arteriolar vasodilator that is effective for hypertensive emergencies associated with pregnancies. The most common adverse effect of hydralazine administration is unpredictable hypotension. Labetalol decreases heart rate and may be preferred because of a lack of reflex tachycardia, hypotension, or increased intracranial pressure. However, the drug of choice for the prevention and control of maternal seizures in patients with severe preeclampsia or eclampsia during the peripartum period is i.v. magnesium sulfate. Therapeutic serum magnesium levels cause cerebral vasodilation, thereby reversing the ischemia produced by cerebral vasospasm during an eclamptic episode. The results of one study indicated that women receiving magnesium sulfate therapy had a 58% lower risk of eclampsia than placebo., Conclusion: Magnesium sulfate remains the drug of choice for the prevention and treatment of preeclampsia. Alternative antihypertensive agents may provide additional benefit in the management of hypertension for preeclamptic patients.

We report three cases of acute pulmonary edema that occurred during treatment by intravenous tocolysis using nicardipine in twin pregnancy patients with no previous heart problems. The three patients were admitted into our unit on account of the risk of premature birth after 29 to 32 weeks of amenorrhea. The treatment by intravenous tocolysis using nicardipine combined with glucocorticoids therapy had been undertaken in the previous maternity ward. The three patients presented symptoms of acute dyspnea 48 hours after the beginning of the treatment. Paraclinical examinations eliminated the diagnosis of pulmonary embolism. The patients'condition improved rapidly with appropriate diuretic treatment and by modifying the tocolysis. There are currently few studies proving the benefits of nicardipine in tocolysis treatment. Few similar cases of acute pulmonary edema have been noted in twin pregnancy patients treated with nicardipine. Haemodynamic modifications specific to twin pregnancy, intravenous hydratation and glucocorticoid maturation may explain a part of this complication. Therefore, it is appropriated to limit the use of intravenous nicardipine in the sole indication of tocolysis in twin pregnancy, and to prefer the use of nifedipine and atosiban, that have proven their effectiveness in this indication.